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Archive for the ‘Genetic Engineering’ Category

Probiotic Yeast Engineered To Produce Beta-Carotene – Technology Networks

Saturday, April 17th, 2021

Researchers have genetically engineered a probiotic yeast to produce beta-carotene in the guts of laboratory mice. The advance demonstrates the utility of work the researchers have done to detail how a suite of genetic engineering tools can be used to modify the yeast.

"There are clear advantages to being able to engineer probiotics so that they produce the desired molecules right where they are needed," says Nathan Crook, corresponding author of the study and an assistant professor of chemical and biomolecular engineering at North Carolina State University. "You're not just delivering drugs or nutrients; you are effectively manufacturing the drugs or nutrients on site."

The study focused on a probiotic yeast called Saccharomyces boulardii. It is considered probiotic because it can survive and thrive in the gut, whereas most other yeast species either can't tolerate the heat or are broken down by stomach acid. It also can inhibit certain gut infections.

Previous research had shown that it was possible to modify S. boulardii to produce a specific protein in the mouse gut. And there are many well-established tools for genetically engineering baker's yeast, S. cerevisiae - which is used in a wide variety of biomanufacturing applications. Crook and his collaborators wanted to get a better understanding of which genetic engineering tools would work in S. boulardii.

Specifically, the researchers looked at two tools that are widely used for gene editing with the CRISPR system and dozens of tools that were developed specifically for modifying S. cerevisiae.

"We were a little surprised to learn that most of the S. cerevisiae tools worked really well in S. boulardii," Crook says. "Honestly, we were relieved because, while they are genetically similar, the differences between the two species are what make S. boulardii so interesting, from a therapeutic perspective."

Once they had established the viability of the toolkit, researchers chose to demonstrate its functionality modifying S. boulardii to produce beta-carotene. Their rationale was both prosaic and ambitious.

"On the one hand, beta-carotene is orange - so we could tell how well we were doing just by looking at the colonies of yeast on a petri dish: they literally changed color," Crook says. "On a more ambitious level, we knew that beta-carotene is a major provitamin A carotenoid, which means that it can be converted into vitamin A by the body - and we knew that vitamin A deficiency is a major public health problem in many parts of the world. So why not try to develop something that has the potential to be useful?"

Researchers tested the modified S. boulardii in a mouse model and found that the yeast cells successfully created beta-carotene in the guts of mice.

"This is a proof of concept, so there are a lot of outstanding questions," Crook says. "How much of this beta-carotene is getting absorbed by the mice? Are these biologically relevant amounts of beta-carotene? Would it work in humans? All of those are questions we'll have to address in future work. But we're excited to see what happens. And we're excited that these tools are now publicly available for use by others in the research community."

Reference:Durmusoglu D, AlAbri IS, Collins SP, et al. In situ biomanufacturing of small molecules in the mammalian gut by probiotic Saccharomyces boulardii. ACS Synth Biol. 2021. doi:10.1021/acssynbio.0c00562

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In the US, Imminent Release of Genetically Modified Mosquitoes To Fight Dengue – The Wire Science

Saturday, April 17th, 2021

This spring, the biotechnology company Oxitec plans to release genetically modified (GM) mosquitoes in the Florida Keys. Oxitec says its technology will combat dengue fever, a potentially life-threatening disease, and other mosquito-borne viruses such as Zika mainly transmitted by the Aedes aegypti mosquito.

While there have been more than 7,300 dengue cases reported in the United States between 2010 and 2020, a majority are contracted in Asia and the Caribbean, according to the US Centres for Disease Control and Prevention. In Florida, however, there were 41 travel-related cases in 2020, compared with 71 cases that were transmitted locally.

Native mosquitoes in Florida are increasingly resistant to the most common form of control insecticide and scientists say they need new and better techniques to control the insects and the diseases they carry. There arent any other tools that we have. Mosquito nets dont work. Vaccines are under development but need to be fully efficacious, says Michael Bonsall, a mathematical biologist at the University of Oxford, who is not affiliated with Oxitec but has collaborated with the company in the past, and who worked with the WHO to produce a GM mosquito-testing framework.

Bonsall and other scientists think a combination of approaches is essential to reducing the burden of diseases and that, maybe, newer ideas like GM mosquitoes should be added to the mix. Oxitecs mosquitoes, for instance, are genetically altered to pass what the company calls self-limiting genes to their offspring; when released GM males breed with wild female mosquitoes, the resulting generation does not survive into adulthood, reducing the overall population.

But Oxitec has been proposing to experimentally release GM mosquitos in the Keys since 2011, and the plan has long been met with suspicion among locals and debate among scientists. Some locals say they fear being guinea pigs. Critics say they are concerned about the possible effects GM mosquitoes could have on human health and the environment. In 2012, the Key West City Commissionobjected to Oxitecs plan; in a non-binding referendum four years later, residents of Key Haven where the mosquitoes would have been released rejected it, while residents in the surrounding county voted in support of the release. With the decision left up to the Florida Keys Mosquito Control District, officials approved the trial to be conducted elsewhere in the Keys.

According to Oxitec, the release was delayed due to a transfer of jurisdiction over the project from the U.S. Food and Drug Administration to the Environmental Protection Agency.

The company reapplied for approval to release a new version of the mosquitoes, called OX5034, in the Keys. In May, the EPA granted a two-year experimental use permit, which the agency can cancel at any time. State and local sign-off soon followed finally giving the project the greenlight.

Oxitecs OX5034 mosquitoes are the first GM mosquitoes approved for release in the US. The company has already conducted a trial with the OX5034 mosquitoes in Brazil and released more than a billion of a previous version, called OX513A, there and in other locations over the years including the Cayman Islands. The company says it is confident in the effectiveness and safety of the technology.

But some scientists want to hit pause on Oxitecs Florida trial, to find what they say is a fairer process in deciding to release the mosquitoes. Others want to see clearer proof that this technology is even necessary, claiming that the company has only released its most positive data with the public and has kept other key data, including whether the mosquitoes curb disease transmission, private. And if the release actually launches as planned, some Keys residents say they aim to interfere.

Critics also say that Oxitec failed to engage with local communities in Florida and get their consent to release the mosquitoes. Whats the most upsetting is that the very people that are going to be most impacted, both by the benefits or the risks of such a decision, have like the smallest voice in how these choices are made. I think thats a really big issue, says Natalie Kofler, a molecular biologist and bioethicist who founded Editing Nature, a platform that advocates for inclusive decision-making processes to steer the use of genetic technology. If Oxitec doesnt do this right, she adds, we could have a huge impact on delaying the use of other beneficial technologies like that in the future.

Oxitecs OX5034 mosquitoes are programmed to combat the transmission of mosquito-borne illnesses by suppressing local Aedes aegypti populations. Oxitec which is US-owned and based in the United Kingdom describes their mosquitoes as friendly because they will only release males, which, unlike females, do not bite humans or transmit disease.

Also read: Clever Approach: Scientists Create GM-Free Organisms Using Genetic Engineering

At Oxitecs laboratory in the UK, the company genetically engineers the mosquitoes, giving the insects the self-limiting gene that makes the females dependent on the antibiotic tetracycline. Without the drug, they will die. Eggs from these genetically-altered mosquitoes which will hatch both male and female insects will be shipped to the Keys. Mosquitoes require water to mature from an egg to an adult; when Oxitecs team adds water to the boxes the mosquitoes will be deployed in, both GM males and GM females will hatch. With no tetracycline present in the box, the GM females are expected to die in early larval stages.

The male mosquitoes will survive and carry the gene. When they leave the boxes, the insects will, hypothetically, fly away to mate with wild females to pass the gene to the next wild generation, according to Nathan Rose, head of regulatory affairs at Oxitec. Kevin Gorman, the companys chief development officer, says the local female mosquito population will be increasingly reduced which will also reduce the number of wild male mosquitoes in the treatment areas.

Gorman emphasised to Undark that the EPA and other regulators found no risk in using tetracycline in breeding their genetically-altered mosquitoes. But some scientists think the presence of this antibiotic in the environment does pose a risk. According to Jennifer Kuzma, co-founder and co-director of the Genetic Engineering and Society Centre at North Carolina State University, tetracyline is commonly used in Florida to prevent bacterial diseases in agriculture particularly in citrus groves and to treat bacteria in sewage plants.

The use of the antibiotic for these purposes may mean that it will remain in the environment, especially in water where the mosquitoes breed, which could allow Oxitecs female mosquitoes to survive. While the company does not plan to release the mosquitos near areas where the antibiotic is used, Kuzma says the EPAs risk assessment did not include testing of any standing water for tetracycline something, she adds, would have been easy enough to do for good due diligence.

Skeptics of Oxitecs GM mosquitoes include local residents, physicians, scientists and environmental activists. Many of these opponents say they arent anti-GMO, but disagree with how the approval process has been handled. One group has even kept a running list of what it sees as Oxitecs wrongdoings since it first began experimental releases. The list includes Oxitecs lack of disease monitoring in the countries where it has released mosquitoes; the unknown price of its technology; and complaints that the company has overstated the success of some of it its trials.

I cannot trust this company. I cannot trust this technology, says Mara Daly, a resident of Key Largo who says shes been following Oxitecs plans for nine years.

This is not a traditional pesticide, she adds. This is not a chemical that you can trace. This is something completely different, new emerging technology, and we need better regulation.

Phil Goodman, chairman of the Florida Keys Mosquito Control District (FKMCD), an independently-elected commission carrying out mosquito control within Monroe County, says that many of those who discredit Oxitecs evidence do not understand the technology. Theyre fear-mongering, he says.

They have very little credibility here in the Florida Keys as far as Im concerned, he adds.

But people like Daly and Barry Wray, executive director of the Florida Keys Environmental Coalition, disagree. We want to know its safe, says Wray, who notes that his group more generally supports GM technology. We dont have another Florida Keys ecosystem. We dont have another Florida Keys community. We have this one.

Daly, Wray, and others point to what they perceive as the FKMCDs disrespect for public opinion. They argue that the community wasnt given a chance to consent before the EPA approval. There was a 30-day public forum in September 2019 about Oxitecs technology application, with 31,174 comments opposing release and 56 in support. A statement emailed to Undark by Melissa Sullivan, an EPA spokesperson, noted that the agency considered these comments during the review, but critics think it happened too quickly to be of real use.

In June, Kofler and Kuzma wrote an opinion piece in The Boston Globe about the EPA approval, critiquing the agencys regulatory system and calling for a better process for evaluating new biotechnologies. The researchers expressed concern that the EPA did not convene an independent, external scientific advisory panel to review Oxitecs claims about its mosquito strategy and that the agency only publicly released its risk assessment after approving the technology. The American public, Kofler and Kuzma wrote, needs to be assured that these decisions are made free of conflicts of interest. The statement from the EPAs Sullivan noted that the agency conducted anextensive risk assessment based on the best available science.

Some critics also wanted there to be more public engagement. Kofler and Kuzma say they offered to provide their expertise, along with other outside experts, to the mosquito control district to allow more discussion about the GM mosquitoes with the Keys community. But Kofler says the district wasnt responsive. Oxitec itself launched webinars about their new product, but not until after the EPA approval. Here we are, like in the final hour, having these conversations that needed to be happening a year ago, says Kofler.

Without public trust and enthusiasm, it doesnt matter whether Oxitecs mosquito technique works, says Guy Reeves, a genetic researcher at the Max Planck Institute for Evolutionary Biology in Germany, who stresses that he doesnt think the companys approach is unsafe. If the population in Florida Keys becomes so sensitised to this issue that they can no longer cooperate with each other thats good for the mosquitoes, not good for the people, he adds.

Based on their first generation mosquito OX513A, Oxitec says it has shown that the approach reduces a targeted mosquito population in trials in both Brazil and the Cayman Islands. But theres no evidence that this new OX5034 mosquito release will actually be worth it for mosquito suppression, says Reeves. Oxitec also hasnt explained how their new mosquito will directly curb human diseases, such as dengue. Reducing disease transmission and burden should be measures of efficacy for this technology, says Kofler.

According to Gorman, independent disease suppression data has only been collected by municipalities in Brazil because thats where most of the companys trials have been released in larger scales. These municipalities have shown that Oxitec mosquitoes have reduced dengue cases in areas of release, Gorman says. In order for Oxitec to collect additional data, he adds, the company needs to release and test large areas over sustained periods of time. Gorman maintains that the company is not required to report formal health impact studies.

Reeves adds that Oxitec also hasnt explained what resources are needed to sustain this product, how long it could take to be effective, or the cost. When asked about the cost of the Florida Keys project, Oxitec responded to Undark by email: Oxitec is a pre-commercial, pre-profit company. We will not profit from this pilot project in Florida. We are paying for it ourselves.

Oxitec has released more than a billion of their OX513A mosquitoes over the past 10 years. According to independent scientists, some of those experiments did not go well.

For example, researchers at Yale University and collaborators from Brazil analysed Oxitecs 2015 release of OX513A in Brazil. The scientists confirmed that some offspring of the genetically modified mosquitoes which were supposed to die and not pass new genes to the wild population survived to adulthood and mated with their native counterparts. Between 10 and 60 percent of the native mosquitoes contained genes from Oxitec, according to the Yale study, which published in Nature in 2019. The papers authors concluded they do not know what impacts these mixed mosquitoes have on disease control or transmission, but added that their findings underscore the importance of monitoring the genetics of the insects.

Oxitec disagreed with the findings and responded on the journals website. Oxitec told Gizmodo that Yales study includes numerous false, speculative, and unsubstantiated claims and statements about Oxitecs mosquito technology. And when Kofler and three other scientists wrote about Oxitecs Brazil trial in The Conversation, Oxitec pushed to have the article retracted, says Kofler.

For this coming release, some Key Largo locals are willing to act on their anger. Daly, for instance, says that if the mosquitoes are deployed in her neighbourhood, shell try to put insecticide in any box she finds or send it to an expert to test even if it means getting in trouble with the federal authorities. I already have my arresting officer and she said shes gonna clean her handcuffs for me, she says. I dont care.

Ideally, Daly says, it wont have to come to that. She and other locals hope to stop Oxitec before the latest mosquitos are delivered. Daly says she has been busy organising protests like one that happened recently in Key Largo and giving out yard signs to residents who dont want their property used in the trial. Locals are pissed off. So I have been busy getting the press to cover the local opposition, Daly wrote in an email to Undark.

The first flying insect or animal that can actually use our human blood for a friggin trial for a product to come to market without my consent, Daly says.

Thats my blood, she adds. Thats my sons blood. Thats my dogs blood.

Taylor White is a freelance journalist based in Cape Cod, MA and a graduate of the Science, Health & Environmental Reporting Program at the NYU school of journalism. Her work has appeared in NOVA GBH, Dana-Farber Cancer Institute, the American Association for the Advancement of Science, GenomeWeb, Spectrum and Science Vs.

This article was originally published on Undark. Read the original article.

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CRISPRoff: A New Addition to the CRISPR Toolbox – Technology Networks

Saturday, April 17th, 2021

Over the past decade, the CRISPR-Cas9 gene editing system has revolutionized genetic engineering, allowing scientists to make targeted changes to organisms DNA. While the system could potentially be useful in treating a variety of diseases, CRISPR-Cas9 editing involves cutting DNA strands, leading to permanent changes to the cells genetic material.

Now, in a paper published online in Cell on April 9, researchers describe a new gene editing technology called CRISPRoff that allows researchers to control gene expression with high specificity while leaving the sequence of the DNA unchanged. Designed by Whitehead Institute Member Jonathan Weissman, University of California San Francisco assistant professor Luke Gilbert, Weissman lab postdoc James Nuez and collaborators, the method is stable enough to be inherited through hundreds of cell divisions, and is also fully reversible.

The big story here is we now have a simple tool that can silence the vast majority of genes, says Weissman, who is also a professor of biology at MIT and an investigator with the Howard Hughes Medical Institute. We can do this for multiple genes at the same time without any DNA damage, with great deal of homogeneity, and in a way that can be reversed. It's a great tool for controlling gene expression.

The project was partially funded by a 2017 grant from the Defense Advanced Research Projects Agency to create a reversible gene editor. Fast forward four years [from the initial grant], and CRISPRoff finally works as envisioned in a science fiction way, says co-senior author Gilbert. It's exciting to see it work so well in practice.

Because these methods alter the underlying DNA sequence, they are permanent. Plus, their reliance on in-house cellular repair mechanisms means it is hard to limit the outcome to a single desired change. As beautiful as CRISPR-Cas9 is, it hands off the repair to natural cellular processes, which are complex and multifaceted, Weissman says. It's very hard to control the outcomes.

Thats where the researchers saw an opportunity for a different kind of gene editor one that didnt alter the DNA sequences themselves, but changed the way they were read in the cell.

This sort of modification is what scientists call epigenetic genes may be silenced or activated based on chemical changes to the DNA strand. Problems with a cells epigenetics are responsible for many human diseases such as Fragile X syndrome and various cancers, and can be passed down through generations.

Epigenetic gene silencing often works through methylation the addition of chemical tags to to certain places in the DNA strand which causes the DNA to become inaccessible to RNA polymerase, the enzyme which reads the genetic information in the DNA sequence into messenger RNA transcripts, which can ultimately be the blueprints for proteins.

Weissman and collaborators had previously created two other epigenetic editors called CRISPRi and CRISPRa but both of these came with a caveat. In order for them to work in cells, the cells had to be continually expressing artificial proteins to maintain the changes.

With this new CRISPRoff technology, you can [express a protein briefly] to write a program that's remembered and carried out indefinitely by the cell, says Gilbert. It changes the game so now you're basically writing a change that is passed down through cell divisions in some ways we can learn to create a version 2.0 of CRISPR-Cas9 that is safer and just as effective, and can do all these other things as well.

Because the method does not alter the sequence of the DNA strand, the researchers can reverse the silencing effect using enzymes that remove methyl groups, a method they called CRISPRon.

As they tested CRISPRoff in different conditions, the researchers discovered a few interesting features of the new system. For one thing, they could target the method to the vast majority of genes in the human genome and it worked not just for the genes themselves, but also for other regions of DNA that control gene expression but do not code for proteins. That was a huge shock even for us, because we thought it was only going to be applicable for a subset of genes, says first author Nuez.

Also, surprisingly to the researchers, CRISPRoff was even able to silence genes that did not have large methylated regions called CpG islands, which had previously been thought necessary to any DNA methylation mechanism.

What was thought before this work was that the 30 percent of genes that do not have a CpG island were not controlled by DNA methylation, Gilbert says. But our work clearly shows that you don't require a CpG island to turn genes off by methylation. That, to me, was a major surprise.

The researchers chose a gene to silence in the stem cells, and then induced them to turn into nerve cells called neurons. When they looked for the same gene in the neurons, they discovered that it had remained silenced in 90 percent of the cells, revealing that cells retain a memory of epigenetic modifications made by the CRISPRoff system even as they change cell type.

They also selected one gene to use as an example of how CRISPRoff might be applied to therapeutics: the gene that codes for Tau protein, which is implicated in Alzheimers disease. After testing the method in neurons, they were able to show that using CRISPRoff could be used to turn Tau expression down, although not entirely off. What we showed is that this is a viable strategy for silencing Tau and preventing that protein from being expressed, Weissman says. The question is, then, how do you deliver this to an adult? And would it really be enough to impact Alzheimer's? Those are big open questions, especially the latter.

Even if CRISPRoff does not lead to Alzheimers therapies, there are many other conditions it could potentially be applied to. And while delivery to specific tissues remains a challenge for gene editing technologies such as CRISPRoff, we showed that you can deliver it transiently as a DNA or as an RNA, the same technology that's the basis of the Moderna and BioNTech coronavirus vaccine, Weissman says.

Weissman, Gilbert, and collaborators are enthusiastic about the potential of CRISPRoff for research as well. Since we now can sort of silence any part of the genome that we want, it's a great tool for exploring the function of the genome, Weissman says.

Plus, having a reliable system to alter a cells epigenetics could help researchers learn the mechanisms by which epigenetic modifications are passed down through cell divisions. I think our tool really allows us to begin to study the mechanism of heritability, especially epigenetic heritability, which is a huge question in the biomedical sciences, Nuez says.Reference:Nuez JK, Chen J, Pommier GC, et al. Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing. Cell. 2021;0(0). doi:10.1016/j.cell.2021.03.025

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A Massive New Gene Editing Project Is Out to Crush Alzheimer’s – Singularity Hub

Saturday, April 17th, 2021

When it comes to Alzheimers versus science, science is on the losing side.

Alzheimers is cruel in the most insidious way. The disorder creeps up in some aging brains, gradually eating away at their ability to think and reason, whittling down their grasp on memories and reality. As the worlds population ages, Alzheimers is rearing its ugly head at a shocking rate. And despite decades of research, we have no treatmentnot to mention a cure.

Too much of a downer? The National Institutes of Health (NIH) agrees. In one of the most ambitious projects in biology, the NIH is corralling Alzheimers and stem cell researchers to come together in the largest genome editing project ever conceived.

The idea is simple: decades of research have found certain genes that seem to increase the chance of Alzheimers and other dementias. The numbers range over hundreds. Figuring out how each connects or influences anotherif at alltakes years of research in individual labs. What if scientists unite, tap into a shared resource, and collectively solve the case of why Alzheimers occurs in the first place?

The initiatives secret weapon is induced pluripotent stem cells, or iPSCs. Similar to most stem cells, they have the ability to transform into anythinga cellular Genie, if you will. iPSCs are reborn from regular adult cells, such as skin cells. When transformed into a brain cell, however, they carry the original genes of their donor, meaning that they harbor the original persons genetic legacyfor example, his or her chance of developing Alzheimers in the first place. What if we introduce Alzheimers-related genes into these reborn stem cells, and watch how they behave?

By studying these iPSCs, we might be able to follow clues that lead to the genetic causes of Alzheimers and other dementiaspaving the road for gene therapies to nip them in the bud.

The iPSC Neurodegenerative Disease Initiative (iNDI) is set to do just that. The project aims to stimulate, accelerate, and support research that will lead to the development of improved treatments and preventions for these diseases, the NIH said. All resulting datasets will be openly shared online, for anyone to mine and interpret.

In plain language? Lets throw all of our new biotech superstarswith CRISPR at the forefrontinto a concerted effort against Alzheimers, to finally gain the upper hand. Its an Avengers, assemble moment towards one of our toughest foesone that seeks to destroy our own minds from within.

Alzheimers disease was first recognized in the early 1900s. Ever since, scientists have strived to find the cause that makes a brain waste away.

The most prominent idea today is the amyloid hypothesis. Imagine a horror movie inside a haunted house with ghosts that gradually intensify in their haunting. Thats the amyloid horrora protein that gradually but silently builds up inside a neuron, the house, eventually stripping it of its normal function and leading to the death of anything inside. Subsequent studies also found other toxic proteins that hang around outside the neuron house that gradually poison the molecular tenants within.

For decades scientists have thought that the best approach to beat these ghosts was an exorcismthat is, to get rid of these toxic proteins. Yet in trial after trial, they failed. The failure rate for Alzheimers treatmentso far, 100 percenthas led some to call treatment efforts a graveyard of dreams.

Its pretty obvious we need new ideas.

A few years ago, two hotshots strolled into town. One is CRISPR, the wunderkind genetic sharpshooter that can snip way, insert, or swap out a gene or two (or more). The other is iPSCs, induced pluripotent stem cells, which are reborn from adult cells through a chemical bath.

The two together can emulate Dementia 2.0 in a dish.

For example, using CRISPR, scientists can easily insert genes related to Alzheimers, or its protection, into an iPSCeither that from a healthy donor, or someone with a high risk of dementia, and observe what happens. A brain cell is like a humming metropolitan area, with proteins and other molecules whizzing around. Adding in a dose of pro-Alzheimers genes, for example, could block up traffic with gunk, leading scientists to figure out how those genes fit into the larger Alzheimers picture. For the movie buffs out there, its like adding into a cell a gene for Godzilla and another for King Kong. You know both could mess things up, but only by watching what happens in a cell can you know for sure.

Individual labs have tried the approach since iPSCs were invented, but theres a problem. Because iPSCs inherit the genetic baseline of a person, it makes it really difficult for scientists in different labs to evaluate whether a gene is causing Alzheimers, or if it was just a fluke because of the donors particular genetic makeup.

The new iNDI plan looks to standardize everything. Using CRISPR, theyll add in more than 100 genes linked to Alzheimers and related dementias into iPSCs from a wide variety of ethnically diverse healthy donors. The result is a huge genome engineering project, leading to an entire library of cloned cells that carry mutations that could lead to Alzheimers.

In other words, rather than studying cells from people with Alzheimers, lets try to give normal, healthy brain cells Alzheimers by injecting them with genes that could contribute to the disorder. If you view genes as software code, then its possible to insert code that potentially drives Alzheimers into those cells through gene editing. Execute the program, and youll be able to observe how the neurons behave.

The project comes in two phases. The first focuses on mass-engineering cells edited with CRISPR. The second is thoroughly analyzing these resulting cells: for example, their genetics, how their genes activate, what sorts of proteins they carry, how those proteins interact, and so on.

By engineering disease-causing mutations in a set of well-characterized, genetically diverse iPSCs, the project is designed to ensure reproducibility of data across laboratories and to explore the effect of natural variation in dementia, said Dr. Bill Skarnes, director of cellular engineering at the Jackson Laboratory, and a leader of the project.

iNDI is the kind of initiative thats only possible with our recent biotech boost. Engineering hundreds of cells related to Alzheimersand to share with scientists globallywas a pipe dream just two decades ago.

To be clear, the project doesnt just generate individual cells. It uses CRISPR to make cell lines, or entire lineages of cells with the Alzheimers gene that can pass on to the next generation. And thats their power: they can be shared with labs around the world, to further hone in on genes that could make the largest impact on the disorder. Phase two of iNDI is even more powerful, in that it digs into the inner workings of these cells to generate a cheat codea sheet of how their genes and proteins behave.

Together, the project does the hard work of building a universe of Alzheimers-related cells, each outfitted with a gene that could make an impact on dementia. These types of integrative analyses are likely to lead to interesting and actionable discoveries that no one approach would be able to learn in isolation, the authors wrote. It provides the best chance at truly understanding Alzheimers and related diseases, and promising treatment possibilities.

Image Credit: Gerd Altmann from Pixabay

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Grammar of the Genome: Reading the Influence of DNA on Disease – Baylor University

Saturday, April 17th, 2021

The human genome has long been a difficult book to read. Modern technological advances have recently opened doors for researchers to begin asking a big question: What parts of our DNA sequences might influence disease? Mary Lauren Benton, Ph.D., recently joined the Baylor Engineering and Computer Science faculty as an assistant professor of bioinformatics, and she is working to answer that question.

Mary Lauren Benton, Ph.D.

If you think of the genome like an instruction manual, Im interested in the grammar, Benton said. Im interested in understanding how short DNA sequences turn genes on and off in different cells and allow for many different outcomes. If we know how a particular sequence influences risk of heart disease, for example, we can use that information to help us guide clinical decisions, whether thats applying different treatments, prescribing different medications or scheduling more preventative care. All of these things can help clinicians to better prioritize and care for patients.

Benton uses computer modeling to look through large data sets of genetic information. Bioinformatics allows for processing of these large data in ways not possible previously, giving room for biological researchers to find patterns and solutions using methods and tools from computer science.

I think of bioinformatics as the intersection of computer science and biology, Benton said. I take tools and methods from computer science, and I apply them to solve fundamental biological questions. We have a lot of really big data sets in biology. The human genome is 3 billion base pairs long, which we cant analyze by hand. The tools from computer science and statistics give us a way to ask questions that we wouldnt be able to otherwise. They open the doors to analyses that would have been impossible even 10 or 20 years ago.

Benton most recently authored The Influence of Evolutionary History on Human Health and Disease, which was published in the Nature Reviews Genetic Journal and takes a look at the evolutionary origins of disease. Being diagnosed with a disease or health problem may feel like a present problem; however, Benton explained that looking at the foundations of a disease is important to understanding how to move forward with treatment.

The foundations and the systems that are involved in disease have really deep evolutionary origins, she said. Cancer might be something that youre diagnosed with today, but the foundation of cancer can be traced back to the idea that we have cells that are able to grow and divide, which also provides the opportunity for tumors to grow.

Benton explained that its important to consider the history of the disease and the systems involved alongside any variants or environmental factors that help to cause the disease. A holistic understanding of disease can influence how patients are treated as well as provide information about how their diseases came to be.

Its not enough to understand whats happening in a person right now or in the last five years, Benton said. Understanding the million-year history of how people got here is equally important to make advances in personalizing medicine, especially genomic medicine. Having that long lens is something that is often lost in the day-to-day operations of a doctors office.

Benton is excited to be evaluating the way that researchers think about decoding genetic information. While a common approach is to think of genes as being able to be turned off or on with a simple switch, that may not be the most accurate approach.

We study these sets of genetic switches and how they turn genes on and off at the right times. Often, we think about these switches working one-at-a-time; the gene is either on or its off, Benton said. But it is much more complicated than that. There are often multiple switches that act more like a dashboard of knobs and dials that all work together to properly tune the output of the genome.

Bentons research is moving toward the development of new models and ways of thinking about how known individual elements are combined and factored into this much larger, more accurate dashboard. Differences based on demographic histories, environmental variables and evolutionary processes all influence the risk of disease in different ways. A better understanding of genomes and how genetic variants relate to disease has major implications for precision medicine.

Its really vital for precision medicine to take into account the full diversity of the human experience. We cant focus on one particular kind of person or one population. People of European ancestry are over-represented in genetic studies, Benton said. Improving diversity and representation in our genomic studies is vital to understanding how the genome relates to disease and to learning how to appropriately treat all of the patients that might walk through the doors of a clinic.

Precision medicine, in some ways, seems futuristic and far-off. But, in other ways, precision medicine is already being used to protect at-risk individuals from diseases like cancer. While widespread precision medicine may not be seen for a long time, research like Bentons plays a role in better understanding disease risk broadly and providing context for clinical solutions moving forward.

Precision medicine is both happening right now and is something that well probably always be working toward, Benton said. There are things that we understand right now about specific genetic variants that might predispose you to a certain kind of breast cancer, for example. We already have diseases that we can test for or treat differently based on someones genotype. But, because the genome is such a complicated thing, walking into the clinic and handing your DNA sequence to the doctor, who would then read it and prescribe the right treatments on the spot, is a goal that well always be working toward. Still, I expect well see big changes in the next five to 10 years given the current rate of progress.

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We cannot let China set the standards for 21st century technologies | TheHill – The Hill

Saturday, April 17th, 2021

The information and biotechnology revolutions have changed our world and will heavily inform the future of society. Whoever controls these technologies controls the future, and whoever controls their standardization controls the technologies. China understands this well. For two decades, it has been working to take over international standardization rulemaking bodies to serve the goals advanced in Made in China 2025 that is, to dominate world manufacturing and then transition to become the center of the worlds technological innovation

The dangers to the United States are already present, and in forms that are not obvious. These include, first, direct-to-consumer genetic testing. China may be using such testing to gain genetic information that permits the identification and tracking of Americans, including U.S. military and intelligence community personnel or their relatives. Second, health monitoring apps are able to provide geolocation data to Chinese entities, which means to the Chinese Communist Party (CCP) and its security services. This provides location data that is valuable on its own and might be compared with data from other sources to reveal key information about Americans. Third, the CCP, in cooperation with Chinese industrial entities on international bodies, are developing and setting international standards for emerging technologies. Chinas influence has grown over the past two decades, and Beijing now possesses leadership roles in standards-drafting technical committees, which means it could shape outcomes to its benefit.

China has formulated a four-step strategy to seek dominance in this area: plan, track, participate and take over. Beijing has boasted that it completed the first three steps and is on the last, which is to develop indigenous standards and to lead international standardization. This means China may be replacing international standards with its own standards, in order to control technologies and the market. In 2017, China revised its standardization law, almost 30 years after its adoption in 1989. It also set up the Standardization Administration of China to implement its strategy in the early 2000s. Chinas standardization strategy also has been incorporated into the Belt and Road Initiative so that, as countries are weaved into this network, they adopt Chinas standards.

Beijing essentially has had the three primary standard-setting international organizations the International Organization for Standardization (ISO), the International Telecommunication Union (ITU) and the International Electrotechnical Commission (IEC) under its influence. Two Chinese government officials currently serve as president of ITU and IEC, and placed Chinas proxy as the head of the ISO after the organization was led by a Chinese official for many years. Meanwhile, Beijing has taken leadership or other influential positions in the International Accreditation Forum (IAF), United Nations Industrial Development Organization (UNIDO), International Civil Aviation Organization (ICAO), American Society for Quality (ASQ) and perhaps others.

Chinas strategy to determine the worlds standards appears to be working. In 2019 alone, China submitted 830 standards proposals to the ITU. According to Zhang Xiaogang, former president of the ISO, China planned to initiate 395 international standards by 2020 but, in actuality, it set 495. Zhang claims that China has made the greatest contribution in the field of international standardization in the past five years. Indeed, China has dominated 5G standard-setting, for example, in the 3rd Generation Partnership Project (3GPP), an organization to develop mobile broadband standards, and 90 percent of standard proposals in the 5G super uplink field is done by China Telecom.

Unfortunately, Western countries fail to see the importance of Chinas strategic move. Zhang states, Whoever leads in standard-setting will be the leader of the technology and the controller of the market. Chinas dominance in 5G standards-setting enables it to avoid the Wests sanctions against its tech giants such as Huawei, continue to expand globally, and to dominate the market. This could be a paramount communication-security problem for the U.S.

Of particular importance is Chinas standardization strategy as identified in China Standards 2035 on international bodies engaged in developing and setting standards for select emerging technologies. These include advanced communication technologies and cloud computing and cloud services. The United States and its allies must ensure that international standards for emerging technologies are not being designed to promote the interests of China. If China is successful, it would lead to the exclusion of other participants; China would be the architect, builder and maintainer of the 21st centurys information technology infrastructure.

Washington must take steps to bolster U.S. public- and private-sector participation in international standards-setting bodies. The U.S. must underscore the dangers of interacting with Chinese firms. The government, particularly the Department of Homeland Security, has called attention to this, but there is little recognition that U.S. firms understand the risks associated. There must be greater awareness of smartphone apps, which should be graded on user privacy and their security from Chinese penetration. And U.S. entities that permit Chinese entities to exploit data should be subject to possible legal action.

A key question of the 21st century is a holdover from the previous century: Which state will control scientific knowledge and its standards? The answer is not yet clear. Thankfully, in the 20th century, the U.S. surpassed Nazi Germany to dominate physics and related sciences and industries, and generated the centurys most fearsome weapon the atomic bomb and its progeny, the hydrogen bomb.

If these revolutionary advances occur within the framework of the U.S.-led liberal international order, we are assured improvements to the well-being of people. But if China leads the scientific and technological revolution, these advances will serve the CCPs inherently malign interests. China will aggressively seize opportunities, particularly in nascent areas where standards are not developed including biotechnology, genetic engineering, energy production and distribution technologies, aerospace, 5G and artificial intelligence.

If China has its way in standards-setting, the communist regime will control these critical technologies and the global supply chain. That means it would dominate the future of the free worlds economy, media and politics. The United States no longer can afford complacency.

Bradley A. Thayer is the co-author of How China Sees the World: Han-Centrism and the Balance of Power in International Politics.

Lianchao Han is vice president of Citizen Power Initiatives for China. After the Tiananmen Square massacre in 1989, he was one of the founders of the Independent Federation of Chinese Students and Scholars. He worked in the U.S. Senate for 12 years, as legislative counsel and policy director for three senators.

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First GMO Mosquitoes to Be Released in the Florida Keys – Singularity Hub

Saturday, April 17th, 2021

This spring, the biotechnology company Oxitec plans to release genetically modified (GM) mosquitoes in the Florida Keys. Oxitec says its technology will combat dengue fever, a potentially life-threatening disease, and other mosquito-borne virusessuch as Zika mainly transmitted by the Aedes aegypti mosquito.

While there have been more than 7,300 dengue cases reported in the United States between 2010 and 2020, a majority are contracted in Asia and the Caribbean, according to the U.S. Centers for Disease Control and Prevention. In Florida, however, there were 41 travel-related cases in 2020, compared with 71 cases that were transmitted locally.

Native mosquitoes in Florida are increasingly resistant to the most common form of control insecticideand scientists say they need new and better techniques to control the insects and the diseases they carry. There arent any other tools that we have. Mosquito nets dont work. Vaccines are under development but need to be fully efficacious, says Michael Bonsall, a mathematical biologist at the University of Oxford, who is not affiliated with Oxitec but has collaborated with the company in the past, and who worked with the World Health Organization to produce a GM mosquito-testing framework.

Bonsall and other scientists think a combination of approaches is essential to reducing the burden of diseasesand that, maybe, newer ideas like GM mosquitoes should be added to the mix. Oxitecs mosquitoes, for instance, are genetically altered to pass what the company calls self-limiting genes to their offspring; when released GM males breed with wild female mosquitoes, the resulting generation does not survive into adulthood, reducing the overall population.

But Oxitec has been proposing to experimentally release GM mosquitos in the Keys since 2011, and the plan has long been met with suspicion among locals and debate among scientists. Some locals say they fear being guinea pigs. Critics say they are concerned about the possible effects GM mosquitoes could have on human health and the environment. In 2012, the Key West City Commissionobjected to Oxitecs plan; in a non-binding referendum four years later, residents of Key Havenwhere the mosquitoes would have been releasedrejected it, while residents in the surrounding county voted in support of the release. With the decision left up to the Florida Keys Mosquito Control District, officials approved the trial to be conducted elsewhere in the Keys.

According to Oxitec, the release was delayed due to a transfer of jurisdiction over the project from the U.S. Food and Drug Administration to the Environmental Protection Agency.

The company reapplied for approval to release a new version of the mosquitoes, called OX5034, in the Keys. In May, the EPA granted a two-year experimental use permit, which the agency can cancel at any time. State and local sign-off soon followedfinally giving the project the greenlight.

Oxitecs OX5034 mosquitoes are the first GM mosquitoes approved for release in the US. The company has already conducted a trial with the OX5034 mosquitoes in Brazil and released more than a billion of a previous version, called OX513A, there and in other locations over the yearsincluding the Cayman Islands. The company says it is confident in the effectiveness and safety of the technology.

But some scientists want to hit pause on Oxitecs Florida trial, to find what they say is a fairer process in deciding to release the mosquitoes. Others want to see clearer proof that this technology is even necessary, claiming that the company has only released its most positive data with the public and has kept other key data, including whether the mosquitoes curb disease transmission, private. And if the release actually launches as planned, some Keys residents say they aim to interfere.

Critics also say that Oxitec failed to engage with local communities in Florida and get their consent to release the mosquitoes. Whats the most upsetting is that the very people that are going to be most impacted, both by the benefits or the risks of such a decision, have like the smallest voice in how these choices are made. I think thats a really big issue, says Natalie Kofler, a molecular biologist and bioethicist who founded Editing Nature, a platform that advocates for inclusive decision-making processes to steer the use of genetic technology. If Oxitec doesnt do this right, she adds, we could have huge impact on delaying the use of other beneficial technologies like that in the future.

Oxitecs OX5034 mosquitoes are programmed to combat the transmission of mosquito-borne illnesses by suppressing local Aedes aegypti populations. Oxitecwhich is US-owned and based in the United Kingdomdescribes their mosquitoes as friendly because they will only release males, which, unlike females, do not bite humans or transmit disease.

At Oxitecs laboratory in the UK, the company genetically engineers the mosquitoes, giving the insects the self-limiting gene that makes the females dependent on the antibiotic tetracycline. Without the drug, they will die. Eggs from these genetically-altered mosquitoeswhich will hatch both male and female insectswill be shipped to the Keys. Mosquitoes require water to mature from an egg to an adult; when Oxitecs team adds water to the boxes the mosquitoes will be deployed in, both GM males and GM females will hatch. With no tetracycline present in the box, the GM females are expected to die in early larval stages.

The male mosquitoes will survive and carry the gene. When they leave the boxes, the insects will, hypothetically, fly away to mate with wild females to pass the gene to the next wild generation, according to Nathan Rose, head of regulatory affairs at Oxitec. Kevin Gorman, the companys chief development officer, says the local female mosquito population will be increasingly reducedwhich will also reduce the number of wild male mosquitoes in the treatment areas.

Gorman emphasized to Undark that the EPA and other regulators found no risk in using tetracycline in breeding their genetically-altered mosquitoes. But some scientists think the presence of this antibiotic in the environment does pose a risk. According to Jennifer Kuzma, co-founder and co-director of the Genetic Engineering and Society Center at North Carolina State University, tetracyline is commonly used in Florida to prevent bacterial diseases in agricultureparticularly in citrus grovesand to treat bacteria in sewage plants. The use of the antibiotic for these purposes may mean that it will remain in the environment, especially in water where the mosquitoes breed, which could allow Oxitecs female mosquitoes to survive. While the company does not plan to release the mosquitos near areas where the antibiotic is used, Kuzma says the EPAs risk assessment did not include testing of any standing water for tetracyclinesomething, she adds, would have been easy enough to do for good due diligence.

Skeptics of Oxitecs GM mosquitoes include local residents, physicians, scientists, and environmental activists. Many of these opponents say they arent anti-GMO, but disagree with how the approval process has been handled. One group has even kept a running list of what it sees as Oxitecs wrongdoings since it first began experimental releases. The list includes Oxitecs lack of disease monitoring in the countries where it has released mosquitoes; the unknown price of its technology; and complaints that the company has overstated the success of some of it its trials.

I cannot trust this company. I cannot trust this technology, says Mara Daly, a resident of Key Largo who says shes been following Oxitecs plans for nine years.

This is not a traditional pesticide, she adds. This is not a chemical that you can trace. This is something completely different, new emerging technology and we need better regulation.

Phil Goodman, chairman of the Florida Keys Mosquito Control District (FKMCD), an independently-elected commission carrying out mosquito control within Monroe County, says that many of those who discredit Oxitecs evidence do not understand the technology. Theyre fearmongering, he says.

They have very little credibility here in the Florida Keys as far as Im concerned, he adds.

But people like Daly and Barry Wray, executive director of the Florida Keys Environmental Coalition, disagree. We want to know its safe, says Wray, who notes that his group more generally supports GM technology. We dont have another Florida Keys ecosystem. We dont have another Florida Keys community. We have this one.

Daly, Wray, and others point to what they perceive as the FKMCDs disrespect for public opinion. They argue that the community wasnt given a chance to consent before the EPA approval. There was a 30-day public forum in September 2019 about Oxitecs technology application, with 31,174 comments opposing release and 56 in support. A statement emailed to Undark by Melissa Sullivan, an EPA spokesperson, noted that the agency considered these comments during the review, but critics think it happened too quickly to be of real use.

In June, Kofler and Kuzma wrote an opinion piece in The Boston Globe about the EPA approval, critiquing the agencys regulatory system and calling for a better process for evaluating new biotechnologies. The researchers expressed concern that the EPA did not convene an independent, external scientific advisory panel to review Oxitecs claims about its mosquito strategy and that the agency only publicly released its risk assessment after approving the technology. The American public, Kofler and Kuzma wrote, needs to be assured that these decisions are made free of conflicts of interest. The statement from the EPAs Sullivan noted that the agency conducted anextensive risk assessmentbased on the best available science.

Some critics also wanted there to be more public engagement. Kofler and Kuzma say they offered to provide their expertise, along with other outside experts, to the mosquito control district to allow more discussion about the GM mosquitoes with the Keys community. But Kofler says the district wasnt responsive. Oxitec itself launched webinars about their new product, but not until after the EPA approval. Here we are, like in the final hour, having these conversations that needed to be happening a year ago, says Kofler.

Without public trust and enthusiasm, it doesnt matter whether Oxitecs mosquito technique works, says Guy Reeves, a genetic researcher at the Max Planck Institute for Evolutionary Biology in Germany, who stresses that he doesnt think the companys approach is unsafe. If the population in Florida Keys becomes so sensitized to this issuethat they can no longer cooperate with each otherthats good for the mosquitoes, not good for the people, he adds.

Based on their first generation mosquito OX513A, Oxitec says it has shown that the approach reduces a targeted mosquito population in trials in both Brazil and the Cayman Islands. But theres no evidence that this new OX5034 mosquito release will actually be worth it for mosquito suppression, says Reeves. Oxitec also hasnt explained how their new mosquito will directly curb human diseases, such as dengue. Reducing disease transmission and burden should be measures of efficacy for this technology, says Kofler.

According to Gorman, independent disease suppression data has only been collected by municipalities in Brazil because thats where most of the companys trials have been released in larger scales. These municipalities have shown that Oxitec mosquitoes have reduced dengue cases in areas of release, Gorman says. In order for Oxitec to collect additional data, he adds, the company needs to release and test large areas over sustained periods of time. Gorman maintains that the company is not required to report formal health impact studies.

Reeves adds that Oxitec also hasnt explained what resources are needed to sustain this product, how long it could take to be effective, or the cost. When asked about the cost of the Florida Keys project, Oxitec responded to Undark by email: Oxitec is a pre-commercial, pre-profit company. We will not profit from this pilot project in Florida.We are paying for it ourselves.

Oxitec has released more than a billion of their OX513A mosquitoes over the past 10 years. According to independent scientists, some of those experiments did not go well.

For example, researchers at Yale University and collaborators from Brazil analyzed Oxitecs 2015 release of OX513A in Brazil. The scientists confirmed that some offspring of the genetically modified mosquitoeswhich were supposed to die and not pass new genes to the wild populationsurvived to adulthood and mated with their native counterparts. Between 10 and 60 percent of the native mosquitoes contained genes from Oxitec, according to the Yale study, which published in Nature in 2019. The papers authors concluded they do not know what impacts these mixed mosquitoes have on disease control or transmission, but added that their findings underscore the importance of monitoring the genetics of the insects.

Oxitec disagreed with the findings and responded on the journals website. Oxitec told Gizmodo that Yales study includes numerous false, speculative, and unsubstantiated claims and statements about Oxitecs mosquito technology. And when Kofler and three other scientists wrote about Oxitecs Brazil trial in The Conversation, Oxitec pushed to have the article retracted, says Kofler.

For this coming release, some Key Largo locals are willing to act on their anger. Daly, for instance, says that if the mosquitoes are deployed in her neighborhood, shell try to put insecticide in any box she finds or send it to an expert to testeven if it means getting in trouble with the federal authorities. I already have my arresting officer and she said shes gonna clean her handcuffs for me, she says. I dont care.

Ideally, Daly says, it wont have to come to that. She and other locals hope to stop Oxitec before the latest mosquitos are delivered. Daly says she has been busy organizing protests like one that happened recently in Key Largoand giving out yard signs to residents who dont want their property used in the trial. Locals are pissed off. So I have been busy getting the press to cover the local opposition, Daly wrote in an email to Undark.

The first flying insect or animal that can actually use our human blood for a friggin trial for a product to come to market without my consent, Daly says.

Thats my blood, she adds. Thats my sons blood. Thats my dogs blood.

This article was originally published on Undark. Read the original article.

Image Credit: Frauke Feind from Pixabay

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Novavax to Participate in University of Oxford Com-COV2 Study Comparing Mixed COVID-19 Vaccine Combinations – BioSpace

Saturday, April 17th, 2021

GAITHERSBURG, Md., April 14, 2021 /PRNewswire/ -- Novavax, Inc. (Nasdaq: NVAX), a biotechnology company developing next-generation vaccines for serious infectious diseases, today announced its participation in a newly expanded investigator-initiated Phase 2 clinical trial called Comparing COVID-19 Vaccine Schedule Combinations Stage 2(Com-COV2), to be conducted by the University of Oxford and supported by the UK Vaccines Taskforce. Novavax' recombinant protein vaccine candidate, NVX-CoV2373, is one of four COVID-19 vaccines that will be studied to evaluate the potential for combined regimens that mix vaccines from different manufacturers to achieve immune protection against COVID-19.

"Novavax' addition to this important study reflects the urgency of finding innovative ways to protect as many people as possible in a dynamic pandemic landscape," said Filip Dubovsky, M.D., Executive Vice President, Chief Medical Officer, Novavax. "The potential utility of pooling public health resources, including all available vaccines, could help us get ahead of an evolving virus."

Com-COV2 will include 1050 adults 50 years of age or older who received their first vaccination during the prior 8-12 weeks. Volunteer study participants will receive one of four different vaccines as a second dose, 350 of whom will be administered NVX-CoV2373. The research will compare the immune system responses from those who receive a heterologous regimen to those who receive a homologous regimen.

"The focus of these studies is to explore whether multiple COVID-19 vaccines can be used more flexibly, with different vaccines being used for the first and second doses," said Matthew Snape, Associate Professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator on the trial. "If we can show that these mixed schedules generate an immune response that is as good as the standard schedules, this could potentially allow more people to complete their COVID-19 immunization course more rapidly."

Under the protocol, which is a designed as a non-inferiority study, participants will be followed for reactogenicity (safety) and immune responses. The UK Medicines and Healthcare products Regulatory Agency (MHRA) and Joint Committee on Vaccination and Immunisation (JCVI) will formally assess the safety and efficacy of any new vaccination regimen before it is made available to the public.

About NVX-CoV2373NVX-CoV2373 is a protein-based vaccine candidate engineered from the genetic sequence of SARS-CoV-2, the virus that causes COVID-19 disease. NVX-CoV2373 was created using Novavax' recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is adjuvanted with Novavax' patented saponin-based Matrix-M to enhance the immune response and stimulate high levels of neutralizing antibodies. NVX-CoV2373 contains purified protein antigen and can neither replicate, nor can it cause COVID-19. In preclinical studies, NVX-CoV2373 induced antibodies that blocked the binding of spike protein to cellular receptors and provided protection from infection and disease. It was generally well-tolerated and elicited robust antibody response in Phase 1/2 clinical testing.

NVX-CoV2373 is being evaluated in two pivotal Phase 3 trials, a trial in the U.K that demonstrated efficacy of 96.4% against the original virus strain and 89.7% overall, and the PREVENT-19 trial in the U.S. and Mexico that began in December 2020. It is also being tested in two ongoing Phase 2 studies that began in August 2020: A Phase 2b trial in South Africa that demonstrated 48.6% efficacy against a newly emerging escape variant, and a Phase 1/2 continuation in the U.S. and Australia.

NVX-CoV2373 is stored and stable at 2- 8C, allowing the use of existing vaccine supply chain channels for its distribution. It is packaged in a ready-to-use liquid formulation in 10-dose vials.

About Matrix-MNovavax' patented saponin-based Matrix-M adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.

About NovavaxNovavax, Inc.(Nasdaq: NVAX) is a biotechnology company that promotes improved health globally through the discovery, development and commercialization of innovative vaccines to prevent serious infectious diseases. The company's proprietary recombinant technology platform combines the power and speed of genetic engineering to efficiently produce highly immunogenic nanoparticles designed to address urgent global health needs. Novavaxis conducting late-stage clinical trials for NVX-CoV2373, its vaccine candidate against SARS-CoV-2, the virus that causes COVID-19. NanoFlu, its quadrivalent influenza nanoparticle vaccine, met all primary objectives in its pivotal Phase 3 clinical trial in older adults and will be advanced for regulatory submission. Both vaccine candidates incorporate Novavax' proprietary saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies.

For more information, visit http://www.novavax.com and connect with us on Twitter and LinkedIn.

Novavax Forward Looking StatementsStatements herein relating to the future of Novavax and the ongoing development of its vaccine and adjuvant products are forward-looking statements. Novavax cautions that these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include those identified under the heading "Risk Factors" in the Novavax Annual Report on Form 10-K for the year ended December 31, 2020, as filed with the Securities and Exchange Commission (SEC). We caution investors not to place considerable reliance on forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this document, and we undertake no obligation to update or revise any of the statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.

Contacts:

InvestorsNovavax, Inc.Erika Schultz | 240-268-2022ir@novavax.com

Solebury TroutJennifer Porcelli | 646-378-2962jporcelli@soleburytrout.com

Novavax MediaAmy Speak | 617-420-2461Laura Keenan | 410-419-5755media@novavax.com

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AmunBio and NorthShore University to Advance Cancer Immunotherapy with Engineered Oncolytic Viruses – OncoZine

Saturday, April 17th, 2021

Washington State-based AmunBio and Chicago-based NorthShore University HealthSystems Research Institute have agreed to collaborate in the development and the commercialization of an innovative technology platform of novel immunotherapeutic oncolytic viruses. AmunBio has an exclusive option to license this technology.

The proprietary platform technology has the potential to generate a strong pipeline of patient-centric next-generation immunotherapeutic oncolytic viruses.

The conceptOncolytic viruses are a form of immunotherapy that uses native or reprogrammed viruses to infect and selectively kill cancerous cells. The concept of using viruses in killing cancer is, however, not new. At the turn of the nineteenth century, when the existence of viruses was first recognized, there has been considerable interest in using viruses as possible agents of tumor destruction.

The use of viruses in cancer treatment was not the result of true understanding and discerning theory of a possible therapy, but rather, was based on the observation that, in some cases, patients diagnosed with cancer or hematological malignancies who contracted an infectious disease went into brief periods of clinical remission

Early case reports emphasized regression of cancers during naturally acquired virus infections, providing the initial basis for clinical trials where body fluids containing human or animal viruses were used to transmit infections to cancer patients.

In one case, in a patient diagnosed with leukemia, it was well recognized that the contraction of influenza produced beneficial effects. And while doctors were not able to report cases where an accompanying infectious disease led to a complete cure of leukemia, they believed that a treatment based upon the causal infection would, potentially, provide an alternative to the hopelessness of the ordinary treatment of leukemia.'[1]

And while in this approach of infecting cancer patients the immune system arrested the impact of the viruses in most cases, and the viruses failed to impact tumor growth, when, in immunosuppressed patients, infection persisted, tumors regressed. However, morbidity as a result of the infection of normal tissues was unacceptably high, ending attempts to develop novel virus-based treatment options.[2]

In the 1950s and 1960s, with the advent of rodent models and new methods for virus propagation, researchers attempted to develop viruses with greater tumor specificity, but success was limited, and, again, most researchers abandoned their research in finding a virus to kill cancer in the 1970s and 1980s. [2]

ResurgenceHowever, more recently, there has been a resurgence of interest in finding viruses that can be used to target and attack tumors that have already formed. Some of these modifiied virusesbut not allare known as oncolytic viruses and represent a promising approach to treating cancer. And today, the development of oncolytic viral therapies, which represents a unique therapeutic paradigm within Immuno-Oncology, is rapidly gaining momentum.

In November 2005 research and development of oncolytic viruses got a welcome boost when Chinese medical regulators approved Shanghai Sunway Biotechs genetically modified adenovirus oncorine (H101). This drug was the worlds first oncolytic viral therapy for the treatment of nasopharyngeal carcinoma in combination with chemotherapy after the phase III clinical trial. At the same time, the company also bought the rights to Onyx-15 (dl1520), an almost identical oncolytic virus* developed by Onyx Pharmaceuticals which was scheduled to be included into phase III clinical trials for lung cancer in 2000.

Onyx-15The development of Onyx-15 began in 1996 when Frank McCormick***, Ph.D. FRS, the co-founder of Onyx Pharmaceuticals and one of the companys biochemists, initiated and led various drug discovery efforts.

McCormick believed that an adenovirus without its E1B gene, which inactivates the host cells p53 gene, would be able to selectively kill cancer cells. He believed that because normal cells harboring the modified virus, the defenseless virus would be subject to p53-mediated cell cycle arrest, preventing the virus from replicating. Cancer cells lacking p53 would be thus be unable to halt viral replication and would be lysed, with multiplied viruses bursting out to infect and destroy the entire tumor.

Unfortunately, while McCormicks hypothesis seemed brilliant, it was also incorrect. Research shoeed that Onyx-15 was not specific for p53-null cells. However, in early human trials, the oncolytic virus still killed tumor cells preferentially and was superior to chemotherapy alone. In its phase III trial with oncorine, Shanghai Sunway Biotech reported a 79% response rate for oncorine plus chemotherapy, compared with 40% for chemotherapy alone.

While various key opinion leaders and experts believe that a completed phase III trial of Onyx-15 would have resulted in FDA approval, the development and phase III clinical trial of the oncolytic virus was suspended when Pfizer acquired Warner-Lambert, Onyxs development partner.

Looking back, if approved, Onyx-15 would, as some experts suggest, been made obsolete by better oncolytic viruses. One of the reasons is that the deletion of E3 limited the potency of Onyx-15. But the suspension of the phase III trial stigmatized the development of oncolytic viruses because, as a result, many researchers inaccurately assumed that Onyx-15 trial failed. In reality, the trial never started.

MelanomaIn 2015, the U.S. Food and Drug Administration (FDA) approved the first oncolytic virus immunotherapy for the treatment of cancer called talimogene laherparepvec or T-VEC (Imlygic; Amgen). The treatment is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Talimogene laherparepvec involves a herpes virus that has been engineered to be less likely to infect healthy cells as well as cause infected cancer cells to produce the immune-stimulating GM-CSF protein.

While in clinical trials and following regulatory approval oncolytic viruses have indeed met the challenge and have become a valuable tool in the anti-cancer armamentarium, there is still much work that needs to be done in the development of novel immunotherapeutic agents based on this approach.

AgreementThe Research Institute has granted an exclusive option to AmunBio covering intellectual property and technology related to an immunotherapeutic oncolytic virus platform. This technology forms the core of AmunBios proprietary, multimodal therapeutic approach utilizing direct destruction of cancer cells and immune system activation.

The technology is based on more than 20 years of research by Prem Seth, Ph.D., Director, Gene Therapy Program at NorthShore, and AmunBios founder and Chief Scientific Officer, and his associates.

AMUN-003The agreement between AmunBio and NorthShore University HealthSystems Research Instituteincludes the development of AMUN-003, an adenovirus-based immunotherapeutic Immuno-Oncology agent, which is being developed for the treatment of multiple solid tumors, including (triple-negative) breast cancer (TNBC) and melanoma, and the ongoing development of additional immunotherapeutic oncolytic viruses.

Following a planned Investigational New Drug (IND) application, which is expected in late 2021/early 2022, AmunBio is planning multiple Phase I clinical trials of AMUN-003 alone or in combination with checkpoint inhibitors.

AmunBios AMUN-003 blocks suppression of the immune response inside the tumor stimulates the recruitment of cancer-killing immune cells and avoids non-specific inflammation. AMUN-003 can be administered both locally as well as systemically.Preclinical studies with AMUN-003 in breast cancer alone, compared to prior oncolytic virus constructs, demonstrated near-complete breast cancer inhibition. [3]

Based on preclinical studies, we believe that AMUN-003 may lead to long-term protection from cancer recurrence, Seth said.

Incidence of cancerWe believe that in the treatment of cancer, there are still not enough new options, noted Cecilia Zapata-Harms, MS, MHA, AmunBio Chief Operations Officer.

While last year, in 2020, the world focused on the SARS-CoV-2 pandemic, more than 9 million people worldwide lost their fight against cancer. *** [4] Among them were more than 600,000 Americans. Our novel viral immunotherapeutic approach may result in significantly more efficacious treatment options, promising to dramatically improve the outcome for many patients diagnosed with cancer, she observed.

We are delighted to be partnering with NorthShore and to be part of ongoing research initiatives to improve the lives of patients, said Zapata-Harms, commenting on research collaboration with the Research Institute.

Breakthrough researchThe Research Institute is the research arm of NorthShore University and supports the organizations core mission to preserve and improve human life through academic excellence and innovative research. The scientists at the research are involved in a wide range of research activities, from lab-based translational research and advanced imaging to clinical trials. As part of this, NorthShore providing the infrastructure and resources for research, which include both administrative and regulatory oversight of investigative studies. The organization has a long history of firsts.

Were humbled by the fact that the same institution, where in the early 1920s George Frederick Dick, MD, and Gladys Henry Dick, MD pioneered the development of a toxin for the prevention of scarlet fever, stands behind our work in developing engineered oncolytic virus for Immuno-Oncology. Its also the same institution where the American pediatrician Louis Wendlin Sauer, MD, in the 1930s, perfected a vaccine used to prevent pertussis (whooping cough), and, more recently, scientists have developed novel treatment options for diseases like MRSA, reducing infection rates through the study of preventative screenings and diagnostic testing, said Andrei R. Shustov, MD, a member of AmunBio Scientific Advisory Board.[5][6]

Oncolytic viruses represent a unique therapeutic approach within Immuno-Oncology and AmunBio platform technology is expected to result in a fundamental shift, augmenting novel treatment modalities compared to, what we believe, is possible today, said, Stephen R. Wachtel, Ph.D., Assistant Vice President, Research Operations at NorthShore.

With the collaboration between the Research Institute and AmunBio were able to address many of the challenges that have prevented previous endeavors from delivering on the full potential of immunotherapeutic oncolytic viruses within Immuno-Oncology, allowing us to discover and develop novel drug candidates for some of the most challenging cancers, Wachtel concluded.

Note*The only difference between the two oncolytic viruses is a slightly larger deletion in H101s E3 gene, which affects immune response**Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Around the world, much work is being done to develop new treatment options.***Today Frank McCormick, Ph.D. FRS, professor in the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center

Clinical trialsSystemic Chemotherapy Combined With Recombinant Human Adenovirus Type 5 and Endostatin Injections for Treatment Malignant Hydrothorax in NSCLC Patients NCT02579564Intraperitoneal Injection of Oncolytic Viruses H101 for Patients With Refractory Malignant Ascites NCT04771676

Highlights of prescribing informationTalimogene laherparepvec (Imlygic; Amgen, Inc) [Prescribing Information]

Reference[1] Kelly E, Russell SJ. History of oncolytic viruses: genesis to genetic engineering. Mol Ther. 2007 Apr;15(4):651-9. doi: 10.1038/sj.mt.6300108. Epub 2007 Feb 13. PMID: 17299401.[2] Data on file AmunBio[3] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021 Feb 4. doi: 10.3322/caac.21660. Epub ahead of print. PMID: 33538338.[4] Dick GF, Dick GH. Scarlet Fever. Edinb Med J. 1934 Jan;41(1):1-13. PMID: 29645766; PMCID: PMC5314226.[5] Pittman M. History of the development of pertussis vaccine. Dev Biol Stand. 1991;73:13-29. PMID: 1778306.

Featured image: A microscopic view of a virus with a depth of field. Photo courtesy: 2020 2021 AmunBio, Inc. Used with permission

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StrideBio Announces a Multi-technology License and Master SRA with Duke University to Advance Next-generation Gene Therapies – BioSpace

Saturday, April 17th, 2021

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- StrideBio, Inc., a leading developer of novel adeno-associated viral (AAV)-based gene therapies, today announced the signing of a multi-technology collaboration with Duke University that will enable novel next-generation gene therapies against a broad range of disorders. StrideBio is advancing multiple products incorporating these technologies with an initial program targeting a novel treatment for the pediatric neurological disorder Alternating Hemiplegia of Childhood (AHC).

The agreements announced today provide StrideBio an exclusive license to multiple technologies that will enable best-in-class next-generation gene therapies developed at Duke University. Included are novel engineered AAV vectors which complement StrideBios existing STRIVETM capsid engineering platform, having been selected through a cross-species evolution that results in significantly enhanced tropism and potency versus AAV9 across a wide range of tissues such as CNS, skeletal and cardiac muscle. Data on these novel vectors were presented by Duke researcher and StrideBio co-founder, Aravind Asokan, Ph.D., at the American Society of Gene & Cell Therapy 23rd Annual Meeting in an abstract titled Cross Species Evolution of Synthetic AAV Strains for Clinical Translation (Gonzalez et al., ASGCT 2020, Abstract 24). In addition, StrideBio has licensed exclusive rights covering a novel use of IgG-degrading enzyme IdeZ to clear neutralizing antibodies in conjunction with AAV gene therapy administration. This innovative approach was recently published by members of the Asokan Lab in a manuscript titled Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme (Elmore et al., JCI Insight, 2020, 5(19): e139881). Finally, StrideBio obtained license rights to a novel gene therapy approach for the treatment of AHC recently published by Duke researcher Mohamad Mikati, M.D., in a manuscript titled AAV Mediated Gene Therapy in the Mashlool, Atp1a3Mashl/+, Mouse Model of Alternating Hemiplegia of Childhood (Hunanyan et al., Human Gene Therapy, February 12, 2021).

Under the Master Sponsored Research Agreement (SRA), StrideBio will fund collaborative work to advance novel gene therapies initially against AHC and other undisclosed targets. AHC is a devastating pediatric neurological disorder with mutations in a causative gene, ATP1A3, that was first identified by a team of Duke University researchers, including Dr. Mikati, in 2012. StrideBio will work closely with Dr. Mikati using a mouse model of AHC developed in his lab to select and rapidly advance a novel gene therapy candidate to the clinic, leveraging the engineered AAV vectors developed by StrideBio along with its manufacturing and translational development capabilities.

The Master SRA between StrideBio and Duke University also provides a framework for additional new programs to be brought under the collaboration. These programs will aim to utilize novel engineered AAV capsids developed by StrideBio to improve potency, evade neutralizing antibodies and enhance specific tropism to tissues of interest. One additional undisclosed program targeting the CNS vasculature has been initiated.

We are very excited to partner with Duke University to advance these technologies that can improve and expand on the potential benefits of gene therapies for patients who desperately need them, stated Sapan Shah, Ph.D., Chief Executive Officer, StrideBio, Inc. We look forward to working together with a fantastic group of Duke researchers and clinicians to bring next-generation AAV-based gene therapies to patients with rare CNS diseases and beyond, starting with Alternating Hemiplegia of Childhood.

This License and Master Sponsored Research Agreement will ensure that these innovative technologies receive the resources and expertise necessary to develop treatments that can ultimately benefit patients. We are delighted to have StrideBio as a partner on this important effort in the gene therapy area, commented Robin Rasor, Executive Director of the Office of Licensing and Ventures, Duke University.

Specific terms were not disclosed, but include equity, upfront and milestone-driven payments, and sponsored research commitments from StrideBio to Duke University, along with royalties on future product sales.

About StrideBio Founded in 2015 based on the groundbreaking research of Mavis Agbandje-McKenna, Ph.D., and Aravind Asokan, Ph.D., StrideBio, Inc., is a fully integrated gene therapy company focused on creating best-in-class genetic medicines with life-changing or curative potential for children and adults. Our proprietary structure-inspired adeno-associated viral (AAV) vector engineering platform (STRIVE) creates unique and differentiated capsids that overcome current limitations of first-generation gene therapies. Key targeted improvements include reduced seroprevalence, improved tropism for specific cell types, liver de-targeting and increased gene transfer efficiency, with the potential for improved safety and reduced doses in the clinic. StrideBio is advancing a robust pipeline of gene therapy candidates enabled by these novel engineered capsids, initially focused on genetically defined CNS and cardiovascular disorders. Combined with our genetic construct design expertise and in-house manufacturing capability at a 1000L scale, we are well positioned to advance novel best-in-class AAV gene therapies. StrideBio is based in a state-of-the-art 40,000-square-foot facility in Research Triangle Park, N.C., which houses our offices, research labs and in-house AAV manufacturing facilities. For more information, please visit http://www.stridebio.com or follow us on LinkedIn.

View source version on businesswire.com: https://www.businesswire.com/news/home/20210414005123/en/

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ThermoGenesis : The History of Cell and Gene Therapy – marketscreener.com

Saturday, April 17th, 2021

Cell and gene therapies are overlapping fields of research and treatments. While both aim to treat and potentially cure diseases, they have slightly differing approaches and have different historical backgrounds. Due to growing interest surrounding this field, the general public still has much to learn and understand about each of these potentially life-saving therapies.

Below, we provide a general overview and brief historical context for each type of therapy.

Cell therapyis the process of replacing damaged or dysfunctional cells with new, healthy ones by transferring live cells into a patient. These can be autologous (also known as self-to-self, using cells from the patient receiving the treatment) or allogeneic (using cells from a donor for the treatment). While this field of treatment has recently begun to expand, some forms of cell therapy like the cancer-treating hematopoietic stem cell transplantation(HSCT) have been in practice for decades.

While many people have heard of bone marrow transplants, few realize that this procedure is a stem cell therapy. While stem cells can be derived from many sources, such as umbilical cord blood and mobilized peripheral blood, bone marrow derived stem cell therapy is the most commonly used today and has been for more than 50 years.

The first transfusion of human bone marrow was given to a patient with aplastic anemia in 1939. After World War II researchers diligently worked to restore bone marrow function in aplasia patients caused by exposure to radiation produced by the atomic bomb. After a decade of work they were able to show, in a mouse model, that aplasia could be overcome by bone marrow treatment.

The first allogeneic HSCT, which led the way to current protocols, was pioneered by E. Donnall Thomas and his team at the Fred Hutchinson Cancer Research Center and reported in the New England Journal of Medicine in 1957. In this study six patients were treated with radiation and chemotherapy and then received intravenous infusion of bone marrow rich stem cells from a normal donor to reestablish the damaged or defective cells. Since then the field has evolved and expanded worldwide. While almost half of HSCT are allogeneic, the majority of HSCT are autologous, the patient's own stem cells are used for treatment, which carries less risk to the patient.

In 1988, scientists discovered that they could derive stem cells from human embryos and grow the cells in a laboratory. These newly derived stem cells, referred to as embryonic stem cells (hESCs), were found to be pluripotent, meaning they can give rise to virtually any other type of cell in the body. This versatility allows hESCs cells to potentially regenerate or repair diseased tissue and organs. Two decades after they were discovered, treatments based on hESCs have been slow in coming because of controversy over their source and concerns that they could turn into tumours once implanted. Only recently, testing has begun as a treatment for two major diseases: heart failure and type 1 diabetes.

In 2006, researchers made a groundbreaking discovery by identifying conditions that would allow some cells to be 'reprogrammed' genetically. This new type of stem cell became known as induced pluripotent stem cells (iPSCs). Since this discovery, the field has expanded tremendously in the past two decades. Stem cell therapies have expanded in use and have been used to treat diseases such as type 1 diabetes, Parkinson's and even spinal cord injuries.

There has also been a growing focus on using other immune cells to treat cancer. Therapies such as CAR T-cellare dependent upon a patient's T-cells, which play a critical role in managing the immune response and killing cells affected by harmful pathogens. These cells are then reengineered to target and kill certain cancerous cells. Several CAR T-cell therapies have been FDA approved, with the first approval being given in 2017 for Yescarta and Kymriah, to be used for the treatment of B-cell leukemia in children and young adults.

Gene therapyis a process that modifies the expression of a gene or alters the biological process of living cells for therapeutic use. This process can take the form of replacing a disease-causing gene with a new, healthy one, inactivating the mutated gene, or introducing a new gene to help the patient's body fight a disease.

While the use of gene therapy to treat humans is fairly new, the science behind it has been used in science for decades. Farmers and geneticists have collaborated for years on crop improvement using cross pollination, genetic engineering and microinjection techniques to create stronger, more resilient crops.

The first human patient to be treated with gene therapy was a four-year old girlsuffering from severe combined immunodeficiencyin 1990. She received treatment for a congenital disease called adenosine deaminase (ADA). Since then, gene therapies have been used to treat diseases such as cancer, cystic fibrosis and hemophilia.In 2017, the FDA gave its first approval of a gene therapy called Luxturna, which is used to treat patients with established genetic vision loss that may result in blindness. Gene therapies are still being studied and developed, with over 1,000 clinical trialscurrently underway.

ThermoGenesis Holdings Inc., is a pioneer and market leader in the development and commercialization of automated cell processing technologies for the cell and gene therapy fields. We market a full suite of solutions for automated clinical biobanking, point-of-care applications and large-scale cell processing and manufacturing with a special emphasis on the emerging CAR-T immunotherapy market. We are committed to making the world a healthier place by creating innovative solutions for those in need.

For more information on the CAR-TXpress multi-system platform, please contact our Sales team.

Disclaimer

Thermogenesis Holdings Inc. published this content on 13 April 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 13 April 2021 07:10:03 UTC.

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EU’s refusal to permit GMO crops led to millions of tonnes of additional CO2, scientists reveal – Alliance for Science – Alliance for Science

Sunday, February 14th, 2021

Europes refusal to permit its farmers to cultivate genetically engineered (GE) crops led to the avoidable emission of millions of tonnes of climate-damaging carbon dioxide, a new scientific analysis reveals.

The opportunity cost of the EUs refusal to allow cultivation of GE varieties of key crops currently totals 33 million tonnes of CO2 per year, the experts say.

This is equivalent to 7.5 percent of greenhouse gas (GHG) emissions from the entire European agricultural sector, or roughly what might be emitted each year by 10-20 coal-fired power stations.

Given that farmers in North and South America adopted GE crops from the late 1990s onward, this analysis implies that over subsequent decades the additional carbon emitted due to the EUs opposition to genetic engineering will likely be in the hundreds of millions of tonnes.

The findings result from from the fact that GE versions of major crops produce a higher yield because they can better resist damage from insects and competition from weeds.

With Europes farmers condemned to lower total agricultural yields because of GE crop non-adoption, more farmland globally has to be kept in production or plowed up which otherwise might be available for forests to sequester carbon in trees and soil.

The new analysis will make uncomfortable reading for environmental groups that have long combined advocacy for climate mitigation with a steadfast opposition to GMOs because it implies that their opposition to genetic engineering might be substantially worsening the climate emergency.

The paper is co-authored by Emma Kovak and Dan Blaustein-Rejto both from the California-based ecomodernist think tank the Breakthrough Institute and Matin Qaim, from the University of Goettingen, Germany. It is published as a pre-print on the bioRxiv server in advance of formal peer review.

The calculation was made by estimating to what extent GHG emissions could have been avoided if the EUs level of adoption of GE varieties of five major crops (maize, soybean, cotton, canola and sugar beet) in 2017 had been equal to that of the United States.

Our results suggest that GHG emissions reductions from the yield increases in GE crops are substantial and should be included in future analyses, writes lead author Kovak.

The researchers also note that their findings are particularly relevant right now because a possible reassessment of the EUs harsh regulatory regime for biotech crops is currently underway.

However the EUs current policy trend pushes in the opposite direction. As Kovak explains, Europes new Farm-to-Fork Strategy under the European Green Deal aims to expand organic farming, which has lower yields and would be associated with significant increases in global GHG emissions through causing land-use change elsewhere.

She concludes: Rather than offshoring environmental damage to other nations, as the European Green Deal does, the EU should increase agricultural productivity through embracing new crop technologies, thus contributing to global environmental benefits.

The authors, however, caution that their assumptions mean that there are substantial uncertainties in the analysis. They assume, for instance, that increased yields in Europe would lead to a proportionate decrease in production elsewhere.

In reality, while the land-sparing effects of crop yield increases are well established, the magnitude can vary widely according to differing circumstances.

However, uncertainties also mean that the estimated annual GHG savings of 33 million tonnes could on the other hand be a big underestimate. In particular, the analysis does not take into account Europes influence on Africa and Asia, where the EUs refusal to allow farmers to cultivate GE crops has been hugely influential.

Nor does it take into consideration what might have happened if crops more widely grown in Europe than in North America in particular wheat and barley had been genetically engineered to allow similar yield improvements as have been seen in maize, cotton and soy.

At the moment no GE varities of wheat or barley are cultivated widely due to intense and long-standing opposition from politicians and anti-GMO activists. If these crops had been available to farmers in standard GE insect- and weed-resistant varieties, Europes agricultural productivity might have increased substantially.

The researchers conclude on a hopeful note, pointing out that new gene editing technologies will likely further increase the diversity of desirable crop-trait combinations. If these crops are permitted in Europe and elsewhere, huge climate mitigation benefits from future GE crops might still be realized.

Image: European Commission

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New species of fly named after Singanallur Tank – The Hindu

Sunday, February 14th, 2021

A new species of fly, which was recently identified by researchers at the Singanallur Tank, has been named after the water body.

The insect was named Asphondylia singanallurensis in the research paper published in the Zootaxa journal in March 2020. The authors said in the paper that they collected the leaves of jujube shrub (Ziziphus jujuba) growing near the Singanallur Tank during their field visits between 2015 and 2018, that contained leaf galls (abnormal growth on leaves) on the surfaces.

The leaves were dissected in a laboratory and the causative agent for the galls was identified to be a fly from the Cecidomyiidae family, which are commonly known as gall midges. Upon further research which also involved DNA sequencing, the insect was confirmed to be a unique species, according to the research paper.

The paper was authored by Duraikannu Vasanthakumar and Radheshyam M. Sharma from Zoological Survey of India (ZSI) - Western Regional Centre (WRC) in Pune, Senthilkumar Palanisamy from the Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur and Vinny R. Peter from Centre for Urban Biodiversity Conservation and Education (CUBE).

Mr. Vasanthakumar, Senior Zoological Assistant at ZSI - WRC Pune, said there were about 396 different species of flies under the Cecidomyiidae family prior to the discovery of this new species. This particular species has only been reported from Singanallur Tank so far, he told The Hindu on Sunday. Despite the abundance of the jujube shrub (ilanthai in Tamil) in the Western Ghats region, this particular fly has not been reported anywhere so far. Further research regarding the ecological parameters and the life cycle of Asphondylia singanallurensis are being carried out, he noted.

According to Ms. Peter, four more insects have been recently found at Singanallur Tank by researchers and efforts to ascertain whether these are unique species are under way.

In 2017, the Coimbatore Corporation declared the 288-acre Singanallur Tank as a biodiversity conservation zone owing to its rich biodiversity.

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Son of Monarchs Pays Homage to the Beauty of Migration – Sierra Magazine

Sunday, February 14th, 2021

To some, a film about a Mexican scientists spiritual transformation into a butterfly may seem strange. But to Alexis Gambis, its personal. Born to a painter and a filmmaker, Gambis rebelled against a career in art. But after completing a PhD in molecular biology and genetics, he sought ways to bridge his academic research with visual storytelling. I was really drawn to biology from an aesthetic and narrative point of view, Gambis told Sierra.

The result is Son of Monarchs, written and directed by Gambis. It is the recipient of the Alfred P. Sloan Prize, awarded to a feature film focused on science and technology, and recently premiered at the 2021 Sundance Film Festival.

The film follows Mendel (played by Tenoch Huerta), an evolutionary biologist who leaves Mexico for New York to study how the genetic engineering tool CRISPR can alter the physical characteristics of butterflies. After discovering that his grandmother has passed away, Mendel travels to Mexico to attend her funeral in Michoacn, home to the Monarch Butterfly Biosphere Reserve. Whats meant to be a two-day visit reconnects him with old friends and family as well as the trauma that drove him away from the place he once called home.

Much of the film unfolds through flashbacks, blurring the lines between Mendels childhood in Michoacn and his life in New York. Son of Monarchs explores Mendels psychic transformation as he reconciles the loss of his parents, the loss of his culture, and ultimately, the loss of himself.

Mendel as a child, played by Kaarlo Isaacs. | Photo courtesy of Sundance Institute/Alexis Gambis

Although Son of Monarchs explores a range of ideas, Gambis weaves them together with subtle precision. The film is layered with sharp observations on science, spirituality, the environment, and migration. The butterfly migrations of Mendels childhood are diminished by deforestation and mining, even as local schoolchildren memorize and reenact the passage of the monarchs from North America to Mexico and perform climate change through folklore dance (the childrens reenactment is based on a real performance that Gambis saw while in Mexico). As the director, I don't want to take a stance and say, Stop destroying the butterfly forest!" Gambis said. I don't want to preach, because I feel that these conversations are so complicated.

In the film, science and spirituality are not juxtaposed but in conversation with one another. When Mendel embraces his animal spirit during an ancestral ceremony or gazes into his microscope to extract butterfly pigment, the goal of understanding the world is the same.

The film conveys the mundanity of lab work without downplaying its wonder. Oftentimes, scientific pursuit and research are separated from the spiritual aspect, Gambis said. But I feel like they're very much connected. The idea of being in a laboratory and trying to understand the building blocks of life and how things work is the utmost kind of spiritual process.

Son of Monarchs avoids the dramatization of planetary disruption thats common in the science fiction genre (think Snowpiercer, Annihilation, and The Martian). There's this obsession with sensationalizing science where it brings you into these dystopian worlds, Gambis said. I love those films, but I feel like there needs to be room for other types of film where the science is the backdrop.... I don't want the character to suddenly say, Oh, I made a discovery! I would rather watch him work in the lab in silence. It's part of who he is. He doesn't need to speak about it.

Just as science is innate to Mendel, so is his hybrid identity as a Latino immigrant living in between cultures. The film expands the definition of what it means to be an immigrant by deviating from reductive tropes of Latin American migration, like the sacrificial immigrant who risks it all for a better life. What you see in films about Latinos and Mexicans is very stereotypical, Gambis said. "It's usually about crossing the border. And here, it's about Mexican scientists who actually return to Mexico and live between worlds."

Mendel talks butterflies with his girlfriend (played by Alexia Rasmussen) in New York City. | Photo courtesy of Sundance Institute/Alexis Gambis

If you go to a research lab today, it's full of people from around the world that come and migrate for work reasons, Gambis said. It's a different type of migration that happens in the US. Mendels story is an intimate look into the emotional consequences that follow a sovereign choice, and its his negotiation between identity and belonging that makes this film so visceral.

Gambis hopes that viewers walk away from Son of Monarchs with a deeper appreciation of how we are all animals, not only within a specific ecosystem but also as creatures who are as dependent on migration as other species. As a Brooklyn-based immigrant who wrestles with the paradox of cultural belongingtorn between his French, Venezuelan, and American identitieshe encourages the audience to think critically about who they are and where they come from.

I hope people understand that migration is fluid, Gambis said. You can leave and come back. Maybe we don't know where Mendel ends up, but he floats like a butterfly. He's in Mexico, hes in New Yorkthere's no permanence. It's all cyclical. Of course, it's a certain type of migration, because there are some [migrants] that can't go back home. But I want to emphasize that in the animal world, migration is cyclical, and I hope people can relate to that, and to embrace that migration is beautiful.

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Podcast: TIME’s 2020 Kid of the Year, Gitanjali Rao – All Together – Society of Women Engineers

Sunday, February 14th, 2021

Get ready to be inspired by our latest SWE podcast with TIMEs 2020 Kid of the Year, Gitanjali Rao. Interviewed by the likes of Angelina Jolie and Ellen DeGeneres, Gitanjali has become quite the starand for good reason. At just 15 years old, this brilliant young innovator has designed and built technology and tools that address serious issues like water contamination, opioid addiction and cyberbullying.

Find our SWE Diverse podcasts on SoundCloud, iTunes, Apple Podcasts and more.

Get to know Gitanjali and her innovations in this SWE Diverse episode, hosted by SWE 2020 Achievement Award recipient Jayshree Seth, chief science advocate at 3M. We promise, itll leave you feeling inspired and eager to help the world through engineering.

Each and every one of us has the power to change the world.

-Gitanjali Rao

Gitanjali Rao was recognized as Discovery Education 3M Americas Top Young Scientist in 2017 and received an EPA Presidential award for inventing her device Tethysan early lead detection tool. Gitanjali is also the inventor of Epionea device for early diagnosis of prescription opioid addiction using genetic engineering, and Kindlyan anti-cyberbullying service using AI and Natural Language processing.

She was honored asForbes30 Under 30 in Science in 2019 andTIMEs Top Young Innovator for her innovations and STEM workshops she conducts globally, which has inspired over thirty-five thousand students in the last two years across four continents. In her sessions, she shares her own process of innovation that can be used by students all over the world. She is an experienced TED speaker and often presents in global and corporate forums on innovation and the importance of STEM.

She is an author of the book, Young InnovatorsGuide to STEM which will release in March 2021, and was recently honored as Time Kid of the Year 2020 for her community service and innovations.

Jayshree Seth, Ph.D., is a Corporate Scientist for 3M Company, headquartered in St. Paul, Minnesota, USA, where she has worked for over 27 years. She holds 70 patents on a variety of innovations, with several others pending. Dr. Seth uses scientific knowledge, technical expertise, and professional experience to advance science and develop new products. She currently leads applied technology development for sustainable industrial products in 3Ms Industrial Adhesives and Tapes Division. She is also 3Ms first-ever Chief Science Advocate and is charged with communicating the importance of science in everyday life, breaking down barriers, and building excitement around STEM careers. She is very passionate about teaching, coaching, mentoring and is a sought-after speaker, globally, on a multitude of topics such as innovation, leadership, and science advocacy. Dr. Seth has been interviewed in national and international media, and she has featured in 3M brand campaigns and commercials.

Dr. Seth is the fourth woman and first woman engineer to attain the highest technical designation of Corporate Scientist at 3M, as well as induction into the 3M Carlton Society, which honors the very best among the scientific community. She is also a certified Design for Six Sigma Black Belt. At 3M, she has served on the CEO Inclusion Council, chaired the Asian and Asian American Employee Network (A3CTION), and serves on the Womens Leadership Forum (WLF) Technical Chapter. She has received numerous 3M excellence awards and a record-setting number of intrapreneurial grants to drive innovation. She was conferred the 2020 Achievement Award from the Society of Women Engineers (SWE), the 2019 International Women & Technologies Le Tecnovisionarieaward for sustainability, the 2020 Woman of Distinction by Girl Scouts River Valley, the 2018 Distinguished Alumni Award from her alma mater in India, and was also among engineers selected to attend the National Academy of Engineerings (NAE) 14th annual U.S. Frontiers of Engineering symposium.

Dr. Seth grew up in Northern India, in the university town of Roorkee, at the foothills of the Himalayas and on the banks of the River Ganges canal. She holds a B.Tech. in chemical engineering from NIT, Trichy, India, and an M.S. and Ph.D. in chemical engineering from Clarkson University, New York. Jayshree is a member of the Engineering Advisory Council for Clarkson University. Dr. Seth has over 15 journal publications based on her graduate work, co-authoring several with her husband, who also works at 3M. They enjoy extending science, creativity, and innovation into their kitchen. They have two adult children. Dr. Seth enjoys experiencing other cultures and she is also an avid reader, writer and poet.

Read SWEs newest publication, The Heart of Science: Engineering Footprints, Fingerprints, & Imprints, written by Jayshree Seth. InThe Heart of Science, Seth discusses the relationship society has with science and engineering and offers her unique perspective on topics surrounding advocacy, interdisciplinary contexts, thoughtful leadership and inclusive progress. She also leans on her childhood experiences, and those of her children, as source material on the lessons she has learned during her career journey.All proceeds from the sale of the book will support the Jayshree Seth Scholarship for Women of Color in STEM. This scholarshipto be awarded annually by the Society of Women Engineerswill support a woman pursuing an undergraduate or graduate degree in a STEM field.

SWE Blog provides up-to-date information and news about the Society and how our members are making a difference every day. Youll find stories about SWE members, engineering, technology, and other STEM-related topics.

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Geoengineering: What could possibly go wrong? Elizabeth Kolbert’s take, in her new book – Bulletin of the Atomic Scientists

Sunday, February 14th, 2021

Editors note: This story was originally published by Grist. It appears here as part of theClimate Deskcollaboration. Elizabeth Kolbert is a former member of the Science and Security Board of the Bulletin of the Atomic Scientists.

In Australia, scientists collect buckets of coral sperm, mixing one species with another in an attempt to create a new super coral that can withstand rising temperatures and acidifying seas. In Nevada, scientists nurse a tiny colony of one-inch long Devils Hole pupfish in an uncomfortably hot, Styrofoam-molded pool. And in Massachusetts, Harvard University scientists research injecting chemicals into the atmosphere to dim the suns lightand slow down the runaway pace of global warming.

These are some of the scenes from Elizabeth Kolberts new book,Under a White Sky, a global exploration of the ways that humanity is attempting to engineer, fix, or reroute the course of nature in a climate-changed world. (The title refers to one of the consequences of engineering the Earth to better reflect sunlight: Our usual blue sky could turn apale white.)

Kolbert, a New Yorker staff writer, has been covering the environment for decades: Her first book,Field Notes from a Catastrophe, traced the scientific evidence for global warming from Greenland to Alaska; her second,The Sixth Extinction, followed the growing pace of animal extinctions.

Under a White Skycovers slightly different ground. Humanity is now, Kolbert explains, in the midst of the Anthropocenea geologic era in whichweare the dominant force shaping earth, sea, and sky. Faced with that reality, humans have gotten more creative at using technology to fix the problems that we unwittingly spawned: Stamping out Australias cane toad invasion with genetic engineering, for example, or using giant air conditioners to suck carbon dioxide out of air and turn it into rock. As Kolbert notes, tongue-in-cheek: What could possibly go wrong?

This interview has been condensed and lightly edited for clarity.

Osaka:Under a White Skyis about a lot of things rivers, solar geoengineering, coral reefs but its also about what nature means in our current world. What got you interested in that topic?

Kolbert: All books have complicated births, as it were. But about four years ago, I went to Hawaii to report on a project that had been nicknamed the super coral project. And it was run by a very charismatic scientist namedRuth Gates, who very sadly passed away about two years ago. We have very radically altered the oceans by pouring hundreds of billions of tons of carbon dioxide into the airand we cant get that heat out of the oceans in any foreseeable timescale. We cant change the chemistry back. And if we want coral reefs in the future, were going to have to counter what weve done to the oceans by remaking reefs so they can withstand warmer temperatures. The aim of the project was to see if you could hybridize or crossbreed corals to get more vigorous varieties.

This ideathat we have to counteract one form of intervention in the natural world (climate change) with another form of intervention (trying to recreate reefs)just struck me as a very interesting new chapter in our long and very complicated relationship with nature. And once I started to think about it that way, I started to see that as a pretty widespread pattern. Thats really what prompted the book.

Osaka: Some of these human interventions to save nature seem hopeful and positiveand others go wrong in pretty epic ways. How do you balance those two types of stories?

Kolbert: The book starts with examples that probably will strike many readers as Okay, that makes sense. That makes sense. But it goes from regional engineering solutions through biotechnology, through gene editing, and all the way up to solar geoengineering. So it kind of leads you down what we might call a slippery slope. And one of the interesting things about these cases is that they will divide up people differently. Even people who consider themselves environmentalists will come down on different sides of some of these technologies. The bind were in is so profound that theres no right answer.

Osaka: So someone who accepts what were doing to save the Devils Hole pupfish might not necessarily accept gene-editing mosquitos or dimming the sun through solar geoengineering.

Kolbert: Exactly. And I think sometimes those linesseemclearer than they are once you start to think about it.

Osaka: At one point in the book, theres a quote that is (apocryphally) attributed to Einstein: We cannot solve our problems with the same thinking we used when we created them. But you dont say whether you agree with that sentiment or not. Is that on purpose?

Kolbert: Yeah, you can read the book and say, Im really glad people are doing these things, and I feel better. Or you can read the book and say, as one scientific quote does, This is a broad highway to hell. And both of those are very valid reactions.

Osaka: When you write about geoengineering, you point out that many scientists conclude that its necessary to avoid catastrophic levels of warming, but that it could also be a really bad ideKolbert Do you think that in 15 or 20 years youll be writing about a geoengineering experiment gone wrong, much as youre writing now about failed attempts to protect Louisiana from flooding?

Kolbert: I might argue about the timescales. Im not sure Ill be reporting on it in 15 years, but I thinkyoumight be reporting on it in 30 years.

At the moment, its still the realm of sci-fi, and Im not claiming to have any particular insight into how people are going to respond in the future. But the case thats made in the book by some very smart scientists is that we dont have very many tools in our toolbox for dealing with climate change quickly, because the system has so much inertia. Its like turning around a supertanker: It takes literally decades, even if we do everything absolutely right.

Osaka: Youve reported on climate change for a long time. How does it feel to see geoengineering being explored as a more valuableand potentially necessaryoption?

Kolbert: Well, one thing I learned in the course of reporting the book was that what we now refer to as geoengineering was actually the very first thing that people started to think about when they first realized we were warming the climate. The very first report about climate change that was handed to Lyndon Johnson in 1965 wasnt about how we should stop emittingit was: Maybe we should find some reflective stuff to throw into the ocean to bounce more sunlight back into space!

Its odd, its kind of almost freakish, and I cant explain it, except to say that it sort of fits the pattern of the book.

Osaka: Theres been a longstanding fight in environmentalism between a technology-will-save-us philosophy and a return-to-nature philosophy. Based on the reporting in this book, do you think that the technology camp has won?

Kolbert: I think the book is an attempt to take on both of those schools of thought. On some level, technologyhaswoneven people who would say dont do geoengineering still want to put up solar panels and build huge arrays of batteries, and those are technologies! But where does that leave us? It goes back to Ruth Gates and the super coral project. There was a big fight among coral biologists about whether a project like that should even be pursued. The Great Barrier Reef is the size of Italyeven if you have some replacement coral, how are you going to get them out on the reef? But Gatess point was, were not returning. Even if we stopped emitting carbon dioxide tomorrow, youre not getting the Great Barrier Reef back as it was in a foreseeable timeframe.

My impulse as an old-school environmentalist is to say Well, lets just leave things alone. But the sad fact is that weve intervened so much at this point that evennot intervening is itself an intervention.

Osaka: Now that we have a US president who takes climate change seriously, do you think we could actually start cutting carbon emissions quickly

Kolbert: I really do want to applaud the first steps that theBiden administration has taken. I think they show a pretty profound understanding of the problem. But the question, and its a big one, is What are the limits? Will Congress do anything? What will happen in theSupreme Court? The United States is no longer the biggest emitter on an annual basis, but on a cumulative basis were still the biggest. And we still dont have resolution on how much carbon dioxdie we can put up there to avoid 1.5 or 2 degrees Celsius (3.6 degrees Fahrenheit) of warming. Those are questions with big error bars. If were lucky, I think we can avoid disastrous climate change. But if were not lucky, were already in deep trouble.

Osaka: Is there anything else you want to say about the book?

Kolbert: It sounds kind of weird after our conversation, but the book was actually a lot of fun to write. It sounds odd when youre talking about a book where the subject is so immensely serious.

Osaka: You mean like when the undergraduates in Australia are tossing each other buckets of coral sperm?

Kolbert: Yes! There is always humor in all these situations. I hope that sense of fun comes through.

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An Introduction to PCR – Technology Networks

Sunday, February 14th, 2021

Polymerase chain reaction (PCR) is a technique that has revolutionized the world of molecular biology and beyond. In this article, we will discuss a brief history of PCR and its principles, highlighting the different types of PCR and the specific purposes to which they are being applied.

In 1983, American biochemist Kary Mullis was driving home late at night when a flash of inspiration struck him. He wrote on the back of a receipt the idea that would eventually grant him the Nobel Prize for Chemistry in 1993. The concept was straightforward: reproducing in a laboratory tube the DNA replication process that takes place in cells. The outcome is the same: the generation of new complementary DNA (cDNA) strands based upon the existing ones.

Mullis used the basis of Sanger's DNA sequencing as a starting point for his new technique. He realized that the repeated use of DNA polymerase triggered a chain reaction resulting in a specific DNA segment's amplification.

The foundations for his idea were laid by a discovery in 1976 of a thermostable DNA polymerase, Taq, isolated from the bacterium Thermus aquaticus found in hot springs.1 Taq DNA polymerase has a temperature optimum of 72 C and survives prolonged exposure to temperatures as high as 96 C, meaning that it can tolerate several denaturation cycles.

Before the discovery of Taq polymerase, molecular biologists were already trying to optimize cyclic DNA amplification protocols, but they needed to add fresh polymerase at each cycle because the enzyme could not withstand the high temperatures needed for DNA denaturation. Having a thermostable enzyme meant that they could repeat the amplification process many times over without the need for fresh polymerase at every cycle, making the whole process scalable, more efficient and less time-consuming.

The first description of this polymerase chain reaction (PCR) using Taq polymerase was published in Science in 1985.2

In 1993, the first FDA-approved PCR kit came to market. Since then, PCR has been steadily and systematically improved. It has become a game-changer in everything from forensic evidence analysis and diagnostics, to disease monitoring and genetic engineering. It is undoubtedly considered one of the most important scientific advances of the 20th century.

The PCR is used to amplify a specific DNA fragment from a complex mixture of starting material called template DNA. The sample preparation and purification protocols depend on the starting material, including the sample matrix and accessibility of target DNA. Often, minimal DNA purification is needed. However, PCR does require knowledge of the DNA sequence information that flanks the DNA fragment to be amplified (called target DNA).

From a practical point of view, a PCR experiment is relatively straightforward and can be completed in a few hours. In general, a PCR reaction needs five key reagents:

DNA to be amplified: also called PCR template or template DNA. This DNA can be of any source, such as genomic DNA (gDNA), cDNA, and plasmid DNA.DNA polymerase: all PCR reactions require a DNA polymerase that can work at high temperatures. Taq polymerase is a commonly used one, which can incorporate nucleotides at a rate of 60 bases/second at 70 C and can amplify templates of up to 5 kb, making it suitable for standard PCR without special requirements. New generations of polymerases are being engineered to improve reaction performance. For example, some are engineered to be only activated at high temperatures to reduce non-specific amplification at the beginning of the reaction. Others incorporate a proofreading function, important, for example, when it is critical that the amplified sequence matches the template sequence exactly, such as during cloning.Primers: DNA polymerases require a short sequence of nucleotides to indicate where they need to initiate amplification. In a PCR, these sequences are called primers and are short pieces of single-stranded DNA (approximately 15-30 bases). When designing a PCR experiment, the researcher determines the region of DNA to be amplified and designs a pair of primers, one on the forward strand and one on the reverse, that specifically flanks the target region. Primer design is a key component of a PCR experiment and should be done carefully. Primer sequences must be chosen to target the unique DNA of interest, avoiding the possibility of binding to a similar sequence. They should have similar melting temperatures because the annealing step occurs simultaneously for both strands. The melting temperature of a primer can be impacted by the percentage of bases that are guanine (G) or cytosine (C) compared to adenine (A) or thymine (T), with higher GC contents increasing melting temperatures. Adjusting primer lengths can help to compensate for this in matching a primer pair. It is also important to avoid sequences that will tend to form secondary structures or primer dimers, as this will reduce PCR efficiency. Many free online tools are available to aid in primer design.Deoxynucleotide triphosphates (dNTPs): these serve as the building blocks to synthesize the new strands of DNA and include the four basic DNA nucleotides (dATP, dCTP, dGTP, and dTTP). dNTPs are usually added to the PCR reaction in equimolar amounts for optimal base incorporation.PCR buffer: the PCR buffer ensures that optimal conditions are maintained throughout the PCR reaction. The major components of PCR buffers include magnesium chloride (MgCl2), tris-HCl and potassium chloride (KCl). MgCl2 serves as a cofactor for the DNA polymerase, while tris-HCl and KCl maintain a stable pH during the reaction.The PCR reaction is carried out in a single tube by mixing the reagents mentioned above and placing the tube in a thermal cycler.The PCR amplification consists of three defined sets of times and temperatures termed steps: denaturation, annealing, and extension (Figure 1).

Figure 1: Steps of a single PCR cycle.

Each of these steps, termed cycles, is repeated 30-40 times, doubling the amount of DNA at each cycle and obtaining amplification (Figure 2).

Figure 2: The different stages and cycles of DNA molecule amplification by PCR.

Let's take a closer look at each step.

The first step of PCR, called denaturation, heats the template DNA up to 95 C for a few seconds, separating the two DNA strands as the hydrogen bonds between them are rapidly broken.

The reaction mixture is then cooled for 30 seconds to 1 minute. Annealing temperatures are usually 50 - 65 C however, the exact optimal temperature depends on the primers' length and sequence. It must be carefully optimized with every new set of primers.

The two DNA strands could rejoin at this temperature, but most do not because the mixture contains a large excess of primers that bind, or anneal, to the template DNA at specific, complementary positions. Once the annealing step is completed, hydrogen bonds will form between the template DNA and the primers. At this point, the polymerase is ready to extend the DNA sequence.

The temperature is then raised to the ideal working temperature for the DNA polymerase present in the mixture, typically around 72 C, 74 C in the case of Taq.

The DNA polymerase attaches to one end of each primer and synthesizes new strands of DNA, complementary to the template DNA. Now we have four strands of DNA instead of the two that were present to start with.

The temperature is raised back to 94 C and the double-stranded DNA molecules both the "original" molecules and the newly synthesized ones denature again into single strands. This begins the second cycle of denaturation-annealing-extension. At the end of this second cycle, there are eight molecules of single-stranded DNA. By repeating the cycle 30 times, the double-stranded DNA molecules present at the beginning are converted into over 130 million new double-stranded molecules, each one a copy of the region of the starting molecule delineated by the annealing sites of the two primers.

To determine if amplification has been successful, PCR products may be visualized using gel electrophoresis, indicating amplicon presence/absence, size and approximate abundance. Depending on the application and the research question, this may be the endpoint of an experiment, for example, if determining whether a gene is present or not. Otherwise, the PCR product may just be the starting point for more complex downstream investigations such as sequencing and cloning.

Thanks to their versatility, PCR techniques have evolved over recent years leading to the development or several different types of PCR technology.

Some of the most widely used ones are:

One of the most useful developments has been quantitative real-time PCR or qPCR. As the name suggests, qPCR is a quantitative technique that allows real-time monitoring of the amplification process and detection of PCR products as they are made.2 It can be used to determine the starting concentration of the target DNA, negating the need for gel electrophoresis in many cases. This is achieved thanks to the inclusion of non-specific fluorescent intercalating dyes, such as SYBR Green, that fluoresce when bound to double-stranded DNA, or DNA oligonucleotide sequence-specific fluorescent probes, such as hydrolysis (TaqMan) probes and molecular beacons. Probes bind specifically to DNA target sequences within the amplicon and use the principle of Frster Resonance Energy Transfer (FRET) to generate fluorescence via the coupling of a fluorescent molecule on one end and a quencher at the other end. For both fluorescent dyes and probes, as the number of copies of the target DNA increases, the fluorescence level increases proportionally, allowing real-time quantification of the amplification with reference to standards containing known copy numbers (Figure 3).

qPCR uses specialized thermal cyclers equipped with fluorescent detection systems that monitor the fluorescent signal as the amplification occurs.

Figure 3: Example qPCR amplification plot and standard curve used to enable quantification of copy number in unknown samples.

Reverse transcription (RT) -PCR and RT-qPCR are two commonly used PCR variants enabling gene transcription analysis and quantification of viral RNA, both in clinical and research settings.

RT is the process of making cDNA from single-stranded template RNA3 and is consequently also called first-strand cDNA synthesis. The first step of RT-PCR is to synthesize a DNA/RNA hybrid between the RNA template and a DNA oligonucleotide primer. The reverse transcriptase enzyme that catalyzes this reaction has RNase activity that then degrades the RNA portion of the hybrid. Subsequently, a single-stranded DNA molecule is synthesized by the DNA polymerase activity of the reverse transcriptase. High purity and quality starting RNA are essential for a successful RT-PCR.

RT-PCR can be performed following two approaches: one-step RT-PCR and two-step RT-PCR. In the first case, the RT reaction and the PCR reaction occur in the same tube, while in the two-step RT-PCR, the two reactions are separate and performed sequentially.

The reverse transcription described above often serves as the first step in qPCR too, quantifying RNA in biological samples (either RNA transcripts or derived from viral RNA genomes).

As with RT-PCR, there are two approaches for quantifying RNA by RT-qPCR: one-step RT-qPCR and two-step RT-qPCR. In both cases, RNA is first reverse-transcribed into cDNA, which is used as the template for qPCR amplification. In the two-step method, the reverse transcription and the qPCR amplification occur sequentially as two separate experiments. In the one-step method, RT and qPCR are performed in the same tube.

Digital PCR (dPCR) is another adaptation of the original PCR protocol.4 Like qPCR, dPCR technology uses DNA polymerase to amplify target DNA from a complex sample using a primer set and probes. The main difference, though, lies in the partitioning of the PCR reactions and data acquisition at the end.

dPCR and ddPCR are based on the concept of limiting dilutions. The PCR reaction is split into large numbers of nanoliter-sized sub-reactions (partitions). The PCR amplification is carried out within each droplet. Following PCR, each droplet is analyzed with Poisson statistics to determine the percentage of PCR-positive droplets in the original sample. Some partitions may contain one or more copies of the target, while others may contain no target sequences. Therefore, partitions classify either as positive (target detected) or negative (target not detected), providing the basis for a digital output format.

ddPCR is a recent technology that became available in 2011.5 ddPCR utilizes a water-oil emulsion to form the partitions that separate the template DNA molecules. The droplets essentially serve as individual test tubes in which the PCR reaction takes place.

The recent development of microfluidic handling systems with microchannels and microchambers has paved the way for a range of practical applications, including the amplification of DNA via PCR on microfluidic chips.

PCR performed on a chip benefits from microfluidics advantages in speed, sensitivity and low consumption of reagents. These features make microfluidic PCR particularly appealing for point-of-care testing, for example, for diagnostics applications. From a practical point of view, the sample flows through a microfluidic channel, repeatedly passing the three temperature zones reflecting the different steps of PCR. It takes just 90 seconds for a 10 L sample to perform 20 PCR cycles.6 The subsequent analysis can then be easily carried out off-chip.

The different PCR approaches all have advantages and disadvantages that impact the applications to which they are suited 7. These are summarized in Table 1.

Approach

Advantages

Limitations

PCR

Easiest PCR to perform

Low cost of equipment and reagents

Several downstream applications (e.g., cloning)

Results are only qualitative

Requires post-amplification analyses that increase time and risk of error

Products may need to be confirmed by sequencing

qPCR

Produces quantitative results

Probe use can ensure high specificity

High analytical sensitivity

Low turnaround time

Eliminates requirements for post-amplification analysis

Requires more expensive reagents and equipment

Less flexibility in primer and probe selection

Less amenable to other downstream product confirmation analyses (such as sequencing) due to the small length of the amplicon

Not suitable for some downstream applications such as cloning

RT-PCR and RT-qPCR

Can be used with all RNA types

RNA is prone to degradation

The RT step may increase the time and potential for contamination

dPCR and ddPCR

Fast

No DNA purification step

Provides absolute quantification

Increased sensitivity for detecting the target in limited clinical samples

Highly scalable

Costly

Based on several statistical assumptions

Microfluidic PCR

Accelerated PCR process

Reduced reagent consumption

Can be adapted for high throughput

Portable device for point-of-care applications

Allows single-cell analysis

Still very new technology

Requires extensive sample preparation to remove debris and unwanted compounds

Restricted choice of materials for the microfluidic device due to high temperatures

Table 1: Key advantages and disadvantages of different PCR approaches.

PCR has become an indispensable tool in modern molecular biology and has completely transformed scientific research. The technique has also opened up the investigation of cellular and molecular processes to those outside the field of molecular biology and consequently also finds utility by scientists in many disciplines.

Whilst PCR is itself a powerful standalone technique, it has also been incorporated into wider techniques, such as cloning and sequencing, as one small but important part of these workflows.

Research applications of PCR include:

Gene transcription -PCR can examine variations in gene transcription among cell types, tissues and organisms at a specific time point. In this process, RNA is isolated from samples of interest, and reverse-transcribed into cDNA. The original levels of RNA for a specific gene can then be quantified from the amount of cDNA amplified in PCR.Genotyping -PCR can detect sequence variations in alleles of specific cells or organisms. A common example is the genotyping of transgenic organisms, such as knock-out and knock-in mice. In this application, primers are designed to amplify either a transgene portion (in a transgenic animal) or the mutation (in a mutant animal).Cloning and mutagenesis- PCR cloning is a widely used technique where double-stranded DNA fragments amplified by PCR are inserted into vectors (e.g., gDNA, cDNA, plasmid DNA). This for example, enables the creation of bacterial strains from which genetic material has been deleted or inserted. Site-directed mutagenesis can also be used to introduce point mutations via cloning. This often employs a technique known as recombinant PCR, in which overlapping primers are specifically designed to incorporate base substitutions (Figure 4). This technique can also be used to create novel gene fusions.

Figure 4: Diagram depicting an example of recombinant PCR.Sequencing- PCR can be used to enrich template DNA for sequencing. The type of PCR recommended for the preparation of sequencing templates is called high-fidelity PCR and is able to maintain DNA sequence accuracy. In Sanger sequencing, PCR-amplified fragments are then purified and run in a sequencing reaction. In next-generation sequencing (NGS), PCR is used at the library preparation stage, where DNA samples are enriched by PCR to increase the starting quantity and tagged with sequencing adaptors to allow multiplexing. Bridge PCR is also an important part of the second-generation NGS sequencing process.Both as an independent technique and as a workhorse within other methods, PCR has transformed a range of disciplines. These include:

Genetic research- PCR is used in most laboratories worldwide. One of the most common applications is gene transcription analysis9, aimed at evaluating the presence or abundance of particular gene transcripts. It is a powerful technique in manipulating the genetic sequence of organisms animal, plant and microbe - through cloning. This enables genes or sections of genes to be inserted, deleted or mutated to engineer in genetic markers alter phenotypes, elucidate gene functions and develop vaccines to name but a few. In genotyping, PCR can be used to detect sequence variations in alleles in specific cells or organisms. Its use isnt restricted to humans either. Genotyping plants in agriculture assists plant breeders in selecting, refining, and improving their breeding stock. PCR is also the first step to enrich sequencing samples, as discussed above. For example, most mapping techniques in the Human Genome Project (HGP) relied on PCR.Medicine and biomedical research- PCR is used in a host of medical applications, from diagnostic testing for disease-associated genetic mutations, to the identification of infectious agents. Another great example of PCR use in the medical realm is prenatal genetic testing. Prenatal genetic testing through PCR can identify chromosome abnormalities and genetic mutations in the fetus, giving parents-to-be important information about whether their baby has certain genetic disorders. PCR can also be used as a preimplantation genetic diagnosis tool to screen embryos for in vitro fertilization (IVF) procedures.Forensic science- Our unique genetic fingerprints mean that PCR can be instrumental in both paternity testing and forensic investigations to pinpoint samples' sources. Small DNA samples isolated from a crime scene can be compared with a DNA database or with suspects' DNA, for example. These procedures have really changed the way police investigations are carried out. Authenticity testing also makes use of PCR genetic markers, for example, to determine the species from which meat is derived. Molecular archaeology too utilizes PCR to amplify DNA from archaeological remains.Environmental microbiology and food safety- Detection of pathogens by PCR, not only in patients' samples but also in matrices like food or water, can be vital in diagnosing and preventing infectious disease.PCR is the benchmark technology for detecting nucleic acids in every area, from biomedical research to forensic applications. Kary Mullis's idea, written on the back of a receipt on the side of the road, turned out to be a revolutionary one.

References1. Chien A, Edgar DB, Trela JM. Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus. J Bacteriol 1976;127(3):1550-57 doi: 10.1128/JB.127.3.1550-1557.1976

2. Saiki RK, Scharf S, Faloona F, et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985;230(4732):1350 doi: 10.1126/science.2999980

3. Arya M, Shergill IS, Williamson M, Gommersall L, Arya N, Patel HRH. Basic principles of real-time quantitative PCR. Expert Review of Molecular Diagnostics 2005;5(2):209-19 doi: 10.1586/14737159.5.2.209

4. Bachman J. Chapter Two - Reverse-Transcription PCR (RT-PCR). In: Lorsch J, ed. Methods in Enzymology: Academic Press, 2013:67-74. doi : 10.1016/B978-0-12-420037-1.00002-6

5. Morley AA. Digital PCR: A brief history. Biomol Detect Quantif 2014;1(1):1-2 doi: 10.1016/j.bdq.2014.06.001

6. Taylor SC, Laperriere G, Germain H. Droplet Digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Scientific Reports 2017;7(1):2409 doi: 10.1038/s41598-017-02217-x

7. Ahrberg CD, Manz A, Chung BG. Polymerase chain reaction in microfluidic devices. Lab on a Chip 2016;16(20):3866-84 doi: 10.1039/C6LC00984K

8. Garibyan L, Avashia N. Polymerase chain reaction. J Invest Dermatol 2013;133(3):1-4 doi: 10.1038/jid.2013.1

9. VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative PCR for gene expression analysis. BioTechniques 2008;44(5):619-26 doi: 10.2144/000112776

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Science Talk – Evolution, cancer and coronavirus how biology’s ‘Theory of Everything’ is key to fighting cancer and global pandemics – The Institute…

Sunday, February 14th, 2021

Image: Charles Darwin's Tree of Life

The 12th of February 2021 marks Sir Charles Darwins 212th birthday a day when biologists and many others remember one of the greatest scientists to have ever lived, whose work and theories transformed biology and the world.

Sir Charles Darwins observations that species adapt through variations passed on from one generation to the next is the basis of modern biology a deceptively simple rule that accounts for all of the variation we see in the natural world.

All organisms, big and small, evolve over time to adapt to the environments they inhabit and the same is true for cancer. Understanding evolution is key to the study of cancer and to developing new treatments for the disease. Its also pretty important when it comes to fighting viruses like Covid-19.

This Darwin Day, we spoke to two of our researchers working in the ICRs Centre for Evolution and Cancer, who are building on Darwins theories of evolution to explore new ways to treat cancer.

The ICR's Centre for Evolution and Cancer aims to apply Charles Darwins principle of natural selection to our understanding of why we develop cancer and why it is so difficult to treat.

Find out more

Dr Alejandra Bruna is leader of the Preclinical Modelling of Paediatric Cancer Evolution Team, and she is trying to find the evolutionary components that drive cancer in children.

The ICR is an internationally leading research centre in the study of cancer in children, and Dr Brunas work focuses on neuroblastoma, the most commonly fatal solid tumour in children, among other solid paediatric cancers.

One of the main features of cancer is genomic instability, with most adult cancers displaying high levels of mutations which cancer is able to exploit for survival.

Following Darwins theories of Natural Selection, each mutation could potentially help a cancer cell adapt to its environment better to survive, with beneficial adaptations being passed on through cell division.

Preventing or targeting mutations is an important way to treat cancer, but childhood cancers often display very few mutations, and researchers like Dr Bruna think that there may be different evolutionary forces at work.

Her research is looking at epigenetic changes in childhood cancer cells changes to genes that arent caused by mutations, but that can turn genes on and off in cells.

Her team are investigating whether these epigenetic changes could be the driver for how neuroblastoma cells evolve, which could explain how cancer cells with very few mutations can adapt and develop resistance to treatments.

Dr Bruna says, If non-genetic evolution plays a role in resistance to therapy in paediatric tumours, then we should be trying to focus on finding treatments that target these non-genetic events.

She is using a technique to barcode cells in samples of neuroblastoma, to trace cell dynamics and epigenetic changes over time, which may identify the triggers for mutations that lead to resistance to treatment.

Finding the epigenetic changes that lead to resistance in neuroblastoma will be a challenge, but if they can show that they happen before mutations occur, this incredibly exciting discovery could open up new avenues for treatment for childhood cancers.

The ICRs Centre for Evolution and Cancer has developed sophisticated computer simulations to model how tumours evolve over time, but recreating the complexity of the disease seen in humans is still a huge challenge.

Diseases like prostate cancer are caused by hundreds of mutations that build up in cancer cells, so to understand how prostate cancer might evolve in patients, tests that help reflect this diversity are needed.

Dr Marco Bezzi leads the Tumour Functional Heterogeneity Team at the ICR, and he is using lab-grown mini-tumours called tumour organoids that more closely resemble cancer as its seen in the clinic, to better understand how prostate cancer evolves.

Dr Bezzi says, The ICRs mathematical modelling is really strong, and you can really follow how tumours develop through evolutionary principles. My research takes a very wet lab approach to complement this, by recreating the heterogeneity and selective pressures that cancer faces. We can then track this experimentally to understand how tumours evolve.

His lab generates biobanks of cancer organoids they use to mix together different mutations and grow tumour organoids with distinct genetic patterns.

These organoids can have several different mutations important to prostate cancer within one tumour, which can be studied in mice to see how these populations evolve.

Like Dr Brunas team, they hope to track how tumours evolve across generations of cancer cells using barcodes, to see which mutations give cells survival advantages and are passed on, and which die out.

Working together with mathematical modelling, ICR scientists can test how simulations of cancer evolution stand up to real-world examples to refine their predictions.

The goal is to use these different tools in the lab to understand how tumours in patients may evolve in response to treatment, so they can suggest new treatments as tumours adapt and help patients survive for longer.

These two examples take very different approaches to cancer evolution, but they show how this fundamental principle of life can be harnessed to learn more about cancer and design better ways to treat the disease.

Image: The ICR's Centre for Cancer Drug Discovery

Dr Bruna and Dr Bezzi have just moved into the ICRs new Centre for Cancer Drug Discovery, where researchers working in cancer evolution benefit from the expertise of their colleagues discovering new cancer drugs.

The building is the first of its kind to host hundreds of scientists from different disciplines under one roof to lead an unprecedented 'Darwinian' drug discovery programme that aims to overcome cancers ability to evolve resistance to drugs and herd it into more treatable forms.

The ultimate aim is to transform cancer into a manageable disease that can be controlled long term and effectively cured.

Dr Bezzi says, As a biotechnologist most of what I do is genetic engineering, so its fantastic to have access to the expertise of my colleagues in drug discovery.

By sharing the same spaces, we can share our expertise and knowledge. I can have those quick conversations about experiments and ask them what might be the best drug for a specific type of disease or for that specific patient. The connection we have to the clinic is amazing and it ensures that my work is studying the right questions to help patients.

In our pioneering Centre for Cancer Drug Discovery, our researchers are now developing a new generation of drugs that will make the difference to the lives of millions of people with cancer.

But we still need your support to help finish equipping the Centre and to continue to fund the exciting work that is now taking place within the building.

Donate now

As the world battles with the coronavirus pandemic, scientists can apply the same evolutionary thinking our researchers use in cancer to overcome Covid-19.

Professor Andrea Sottoriva, Director of the Centre for Evolution and Cancer in the Centre for Cancer Drug Discovery, says: Evolutionary biology is one of the most important theories of biology, in the same way that we have general relativity in physics. The theory of evolution allows us to make sense of the observations we see in biology and medicine more widely, and this is also true for the pandemic.

We understand how viruses evolve through the lens of evolutionary biology and we design new vaccines that combat the evolution of viruses to adapt and survive, like what we regularly see in the flu.

The variants we are now seeing in Covid-19 are evidence of the fundamental mechanisms that drive how all organisms evolve, including cancer.

Not every variation provides a survival advantage to viruses, making viruses more contagious or more resilient, and viruses often need a number of significant changes before vaccines will no longer work, but by studying how they change and evolve, doctors can attempt to get ahead of new variants with improved vaccines, helping curb transmission and save lives.

Dr Bruna said: Just like cancer, viruses are made of genetic material, and so they will evolve adaptations that are beneficial to the virus. But scientists will be expecting this and they are monitoring variations in the virus that are occurring.

With cancer the rules are exactly the same, and our researchers are coming up with new ways to model the disease's evolution and to find the triggers that help cancer develop.

And so, despite the death of Sir Charles Darwin more than 130 years ago, the impact of his work lives on and acts as inspiration for researchers around the world, and will continue to do so for generations to come.

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Science Talk - Evolution, cancer and coronavirus how biology's 'Theory of Everything' is key to fighting cancer and global pandemics - The Institute...

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22nd Century Group and KeyGene Launch Advanced Cannabis Technology Platform for Accelerated Development of New Varieties of Hemp/Cannabis Plants with…

Sunday, February 14th, 2021

WILLIAMSVILLE, N.Y., Feb. 10, 2021 (GLOBE NEWSWIRE) -- 22nd Century Group, Inc. (NYSE American: XXII), a leading plant-based, biotechnology company focused on tobacco harm reduction, very low nicotine content tobacco, and hemp/cannabis research, announced today that it has developed and launched a new, cutting-edge technology platform that will enable the Company and its strategic partners to quickly identify and incorporate commercially valuable traits of hemp/cannabis plants to create new, stable hemp/cannabis lines. The platform incorporates a suite of proprietary molecular tools and a large library of genomic markers and gene-trait correlations. The platform was developed in collaboration with researchers at KeyGene, a global leader in plant research involving high-value genetic traits and increased crop yields.

This is a major breakthrough. Quickly and easily identifying the genes responsible for specific traits in a plant is a powerful tool for 22nd Century Group and the hemp/cannabis industry as a whole, said James A. Mish, chief executive officer of 22nd Century Group. That is why we are even now beginning discussions to license this platform to strategic partners to help them improve their plant breeding techniques and to optimize their hemp/cannabis cultivars. We continue to make great advancements through our partnership with KeyGene, and this newly developed molecular breeding platform has the potential to result in exponential growth for the Companys revenues and create new value opportunities for our stakeholders, including shareholders.

Using traditional breeding techniques, it typically takes at least eight to ten years to develop new varieties of hemp/cannabis plants that consistently express important traits, said Juan Sanchez Tamburrino, Ph.D., vice president of research and development at 22nd Century Group. Our new molecular breeding platform can dramatically reduce our development time for new high-value varieties of hemp/cannabis and allows 22nd Century scientists to identify plant lines that carry high levels of major therapeutic cannabinoids, such as cannabidiol (CBD), cannabichromene (CBC), and other minor therapeutic cannabinoids, like cannabidivarin (CBDV) and tetrahydrocannabivarin (THCV).

Demonstrating how this technology can be used, 22nd Century and KeyGene scientists can now accelerate the selection of specific traits yielding novel cannabinoid profiles. For example, the team was able to select specific markers that predict the gender of hemp/cannabis plants with an astounding 99.6% accuracy.

Using this new breeding technology, 22nd Century has already characterized millions of high-value single nucleotide polymorphisms (SNPs). SNPs are molecular markers or guideposts within a plants genome that indicate important variations in Deoxyribonucleic acid (DNA) sequences. Targeting these newly identified SNPs, 22nd Century was able to locate and isolate specific sections of genetic code from genome assemblies present in the Companys state-of-the-art hemp/cannabis bioinformatics database. 22nd Centurys bioinformatics database continues to grow and already contains hundreds of hemp/cannabis genomes and thousands expression datapoints across a wide array of hemp/cannabis varieties and phenotypes. The ability to identify specific genetic variations allows researchers to isolate high-value traits, like increased CBD or tetrahydrocannabinol (THC) production, and then introduce those traits in new plant lines using modern plant breeding techniques, including trait tracking using molecular marker profiles and the Companys proprietary accelerated breeding pipeline.

Since reporting third quarter earnings, 22nd Century has refocused its hemp/cannabis strategy to target the upstream segments of the cannabinoid value chain, in particular, in the areas of plant biotechnology research, gene modification and engineering, modern plant breeding and development, and extraction. The Company intends to build upon its core strengths in the plant science and ingredient value chain and is in advanced discussions with operational partners that will enable it to offer comprehensive commercial breeding, cultivation, and extract purification services utilizing its proprietary hemp/cannabis plants in development. The Company will continue to focus on and ensure the accelerated delivery of valuable, commercial plant lines and technology, and related intellectual property for the life science, consumer product, and pharmaceutical markets.

About 22nd Century Group,Inc.22nd Century Group, Inc. (NYSE American: XXII) is a leading plant biotechnology company focused on technologies that alter the level of nicotine in tobacco plants and the level of cannabinoids in hemp/cannabis plants through genetic engineering, gene-editing, and modern plant breeding. 22nd Centurys primary mission in tobacco is to reduce the harm caused by smoking through the Companys proprietary reduced nicotine content tobacco cigarettes containing 95% less nicotine than conventional cigarettes. The Companys primary mission in hemp/cannabis is to develop and commercialize proprietary hemp/cannabis plants with valuable cannabinoid profiles and desirable agronomic traits.

Learn more atxxiicentury.com, on Twitter@_xxiicenturyand onLinkedIn.

Cautionary Note Regarding Forward-Looking StatementsExcept for historical information, all of the statements, expectations, and assumptions contained in this press release are forward-looking statements. Forward-looking statements typically contain terms such as anticipate, believe, consider, continue, could, estimate, expect, explore, foresee, goal, guidance, intend, likely, may, plan, potential, predict, preliminary, probable, project, promising, seek, should, will, would, and similar expressions. Actual results might differ materially from those explicit or implicit in forward-looking statements. Important factors that could cause actual results to differ materially are set forth in Risk Factors in the Companys Annual Report on Form 10-K filed on March 11, 2020 and in its subsequently filed Quarterly Report on Form 10-Q. All information provided in this release is as of the date hereof, and the Company assumes no obligation to and does not intend to update these forward-looking statements, except as required by law.

Investor Relations & Media Contact:Mei KuoDirector, Communications & Investor Relations22nd Century Group, Inc.(716) 300-1221mkuo@xxiicentury.com

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22nd Century Group and KeyGene Launch Advanced Cannabis Technology Platform for Accelerated Development of New Varieties of Hemp/Cannabis Plants with...

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Researchers create rice that captures more CO2 with 30 percent more yield – FoodIngredientsFirst

Tuesday, February 9th, 2021

09 Feb 2021 --- Scientists in China and Japan have developed a method to increase paddy field-grown rice yield by over 30 percent while sequestering more CO2 and using less fertilizer than traditional varieties.

Researchers at Nagoya University in Japan and Nanjing Agricultural University in China achieved this functionality by increasing the expression of the plasma membrane proton pump gene OSA1 in the rice plant, which was previously found to influence stomatal opening.

CO2 intake in plants occurs exclusively through the stomata, which are holes on the leaves' surface.

By increasing nutrient uptake and stomatal opening, the researchers were able to increase the rate of photosynthesis thereby speeding up growth and yield with less resources.

This new genetics-based approach detailed in Nature could improve crop efficiency for more types of plants to increase the food supply while mitigating the overproduction of CO2.

Click to EnlargeRice with the overexpressed OSA1 gene had a 25 percent increase in its CO2 storage capacity compared to wild rice.New functionalityThe group of scientists found the proton pump overexpressed rice, when compared to a wild strain, took up over 20 percent more mineral nutrients through its roots and opened its stomata over 25 percent wider when exposed to light.

On further analysis, they found that its carbon dioxide storage capacity (the indicator of photosynthesis activity) increased by over 25 percent. Its dry weight (biomass) increased by 18 to 33 percent in hydroponic laboratory growth.

Testing rice in the fieldWith this determined, the researchers set out to find if the results could be replicated under realistic growing conditions.

They conducted yield measurement exercises at four separate rice farms over the course of two years, finding that the rice with the overexpressed OSA1 gene had a yield over 30 percent higher than that of the wild strain.

They also discovered that even if the level of nitrogen fertilizer was reduced by half, it still produced a greater yield than the wild strain did with normal levels of nitrogen.

Capturing more CO2As they take in mineral nutrients such as nitrogen, phosphorus and potassium through their roots, plants simultaneously absorb carbon dioxide through the stomata on their leaves and grow through photosynthesis.

Photosynthesis enables, not only the farming of plants for food, but the exchange of carbon dioxide and management of the earths environment.

While these early-stage models have been created through genetic modification (GM), the researchers anticipate that future generations will use genome editing or chemical engineering instead.

Edited by Missy Green

To contact our editorial team please email us at editorial@cnsmedia.com

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