StemCell Therapy

In a little-noticed study published earlier this year, scientists from Oregon Health & Science University reported the birth of three mouse pups that had been created with a never-before-used recipe for reproduction. Using a common cloning technique, researchers removed the genetic material from one females eggs and replaced them with nuclear DNA from the skin cells of another. Then with a novel chemical cocktail, they nudged the eggs to lose half their new sets of chromosomes and fertilized them with mouse sperm.

In a big step toward achieving in vitro gametogenesis one of reproductive medicines more ambitious moonshots the group led by pioneering fertility researcher Shoukrat Mitalipov now intends to use the same method to make artificial human embryos in a test tube.

If successful, the research holds enormous potential for treating infertility, preventing heritable diseases, and opening up the possibility for same-sex couples to have genetically related children.

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Its one of those high-risk, high reward type of projects, said Paula Amato, an OB-GYN and infertility specialist at OHSU who collects the human eggs used in Mitalipovs experiments. We have no idea yet if it will work, but age-related fertility decline remains an intractable problem in our field, so were eternally grateful to these private funders who are filling a real need here.

Mitalipov directs the Center for Embryonic Cell and Gene Therapy at OHSU. Established in 2013, the center focuses on combining assisted reproductive technologies with genetic correction techniques, with the goal of one day preventing inherited disease.

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The groups work on in vitro gametogenesis (IVG) in human cells is being made possible by an award from Open Philanthropy a grant-making organization primarily funded by Facebook co-founder Dustin Moskovitz and his wife Cari Tuna which will supply the researchers with $4 million over the next three years. The infusion of funds and the involvement of a scientist as storied as Mitalipov makes the ethical and legal questions surrounding mass egg and sperm production more urgent, experts told STAT.

In the U.S., there are no federal laws that prohibit this type of IVG work. However, Congress has barred any research that creates, destroys, or knowingly harms human embryos from receiving federal funding. At the state level, laws governing human embryo research vary widely with 11 states banning it entirely, five states expressly permitting it, and a lot of gray areas in between.

For IVG to move from the research lab to a fertility clinic would require permission from the Food and Drug Administration. Its still unclear if thats something the agency would be able to consider a spending bill rider currently prevents the FDA from receiving any requests to pursue clinical trials involving starting pregnancies with embryos that have been genetically manipulated. In 2019, Congress considered modifying the ban, following a push from scientists and advocates of mitochondrial replacement therapy, also known as three-person IVF, but ultimately renewed it. Mitochondrial replacement therapy is a procedure that combines genetic material from an egg and sperm with mitochondria from a female donor.

Somatic cell nuclear transfer for IVG could fall under the same provision, if the somatic DNA and the egg came from different people. But if they came from the same person, that might represent a loophole.

Some bioethicists worry that the easy availability of IVG could usher in a new era of eugenics, scenarios where prospective parents could create large numbers of embryos and use genetic tools to select the best one. IVG also raises the specter of nonconsensual parenthood something most state laws are currently ill-equipped to handle.

Should this become clinically available, there will be legitimate questions about whose cells can be used and under what conditions that will need regulatory answers, said Hank Greely, director of the Stanford Center for Law and Bioscience, whose book, The End of Sex, examines the future of in vitro gametogenesis. Will that happen? We dont know. But Mitalipov has certainly proven himself a bold and creative scientist, and from my perspective, having his group join the effort to help people who want to have genetic babies but cant is a good thing, provided they can do it safely and effectively.

Mitalipovs lab has long been an incubator for envelope-pushing science. In 2009, he and his colleagues figured out a way to swap out glitchy mitochondrial DNA for healthy versions in the egg cells of monkeys a groundbreaking advance that paved the way for mitochondrial replacement therapy in humans. In 2013, they created lines of embryonic stem cells from cloned human embryos for the first time. A few years later, they became the first team in the U.S. to attempt to correct a genetic mutation in viable human embryos using CRISPR.

But until recently, in vitro gametogenesis, or IVG, wasnt on his to-do list.

Gametes are the cells capable of giving rise to future generations: sperm and eggs. The idea behind IVG is to produce those kinds of cells in test tubes, rather than inside a developing animals body.

In recent years, scientists have made headlines producing artificial gametes from induced pluripotent stem cells. But Mitalipovs group plans to revive a much older technology, which saw some early success in IVG before being abandoned: somatic cell nuclear transfer.

Somatic cell nuclear transfer was pioneered by researchers at the Roslin Institute in Scotland. After they succeeded in using the technique to clone the first mammal a sheep named Dolly scientists realized it might be used to generate artificial gametes, if they could overcome a few additional hurdles.

In cloning, the emptied egg receives a full set of chromosomes from the somatic cell donor and is stimulated in the lab to make it start dividing. Any offspring that result will be genetically identical to that somatic cell.

The procedure for making an artificial oocyte is technically similar to cloning, but would generate unique individuals after fertilization with sperm. However, in order for any resulting embryos to have the right number of chromosomes, the donor DNA has to be cut in half, a process known as haploidization. Oocytes are equipped with the machinery to make that adjustment, if the somatic DNA is introduced at the right phase of their cell cycle.

In 2000, four years after Dolly was born, researchers in Spain generated the first human artificial oocytes using this method. They fertilized three of them, and froze the resulting embryos at the two-cell stage. The plan was to transfer the frozen embryos to the uterus of a woman who had been unable to conceive, and consented to having her somatic DNA slipped into donor eggs as a last-ditch attempt to have genetically related children with her husband.

But when the same protocol was tested in mice where its effects could be examined more closely the chromosomes didnt separate as intended. Shortly thereafter, somatic cell nuclear transfer for human reproduction was banned in many countries, including Spain.

The IVG field moved on, buoyed by the discovery a few years later of a method for taking any kind of cell and rewinding its developmental clock to a more primitive state. With the right chemical cues, a team of Japanese scientists nudged these pluripotent stem cells to produce functional gametes in mice; first sperm in 2011, then eggs, five years later. But they struggled to generate similar results in humans.

In 2018, the group succeeded for the first time in making immature human eggs from scratch. But the process wasnt very efficient and it involved incubating the human stem cells in mini-ovaries theyd created in the lab from mouse embryonic cells a resource-intensive process not exactly suited to mass manufacturing.

So when a post-doc at OHSU named Eunju Kang proposed revisiting the idea of somatic cell nuclear transfer for IVG, Mitalipov was initially skeptical. But data from her initial mouse experiments proved persuasive. Mitalipov threw his support behind the project, and teamed up with a group at Weill Cornell Medicine in New York, including reproductive endocrinologist Gianpiero Palermo, who had successfully generated artificial human oocytes using cloning technology back in 2002. They published the results of their mice experiments in Nature Communications Biology in January.

The OHSU team is now adapting those methods to see if they can generate artificial human eggs with properly separated chromosomes. If successful, they plan to then fertilize those eggs with sperm and grow the resulting embryos in the lab for five or six days to see if they develop normally.

They are betting that this method, while older, will prove better than the induced pluripotent stem cell technologies currently being advanced by artificial egg-making start-up outfits like Conception, Ivy Natal and Gameto.

That approach requires the cells to be cultured for months rather than days, which can lead to epigenetic programming errors and chromosomal instability. Mitalipov also believes that starting with natural eggs will make it easier to strip the donor DNA of its cellular memory and return it to the primitive state known as totipotency a critical step in enabling the embryo to eventually develop all the specialized tissues that make up a human body.

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Researchers revive abandoned technique in effort to make artificial human eggs in a test tube - STAT

SACRAMENTO, Calif. The steel-bar cells inside the courtrooms of Sacramento County Main Jails Patino Justice Center and Gordon Schaber Courthouse are some of the busiest spaces in a bustling Sacramento Superior Court. The cells are as much a part of the courtrooms as the judges bench or jurors box.

Eight courtrooms in all have cells within their courtrooms: Departments 4, 5, 8 and 9 on the second floor of the Schaber Courthouse at 720 9th St., and Departments 60 through 63 in the main jails Patino courts on I Street.

But as the framework of a towering new 17-story, 53-courtroom courthouse rises behind the jail courts near the citys Railyard district, lingering questions of the cells utility, and resultant issues of equity, fairness and attorney access have re-emerged.

The lock-and-key bays will soon give way to plexiglass docks at the new Sacramento County Courthouse, scheduled to be completed in November 2023, but concerns remain. Schematics of the new Sacramento courthouse provided to The Sacramento Bee by court officials give a preview of courtrooms and in-court confinement.

Six courtrooms will have arraignment docks within the courtroom. Each will be approximately 20 feet wide by 6 feet deep, the schematics show; Schabers and Patinos bars replaced with the new facilitys plexiglass.

Its incredibly prejudicial for people viewing it family, neighbors, victims, said Sacramento attorney and former federal public defender Mark Reichel. Hes in orange. Hes in a cage. Hes like some kind of monster.

Criminal defendants are granted the right under the Constitution to confront accusers and witnesses against them in criminal proceedings. The Judicial Council of Californias standards for the states trial court facilities lay out clear objectives for transporting and accommodating defendants held in custody while in the courthouse.

Provide a safe and secure environment for transporting and accommodating jail inmates while in the courthouse.

Maintain the safety and welfare of the judiciary, court staff and public in the courthouse.

Prevent contraband from coming into the building.

The Sheriffs Office manages all in-custody holding and sets protocols for how inmates are held.

Courthouses must be a safe harbor to which members of the public come to resolve disputes that often are volatile. Once courthouses themselves are perceived as dangerous, the integrity and efficacy of the entire judicial process are in jeopardy, Ronald M. George, former chief justice of California, once said.

But the arraignment cells, whether steel bars or a plexiglass box, also expose troubling equity concerns, striking an unfair balance between safety and defendants rights, defense attorneys and criminal justice advocates say.

Each day, a steady stream of orange-clad county inmates held on suspicion of minor offenses to more serious crimes stand, for lack of bail, inside the 7-by-3-foot cages of the existing Sacramento courts. They consult briefly through the bars with their attorneys, await a judges reading of the charges they face, the date of their next court appearance or, if they have entered a plea, the sentence they will receive.

A printed sign taped to the bars warns spectators: No communication of any kind with inmates. Its against the law.

In Sacramento Superior Court, poor or indigent in-custody defendants who cannot post bail make their initial court appearances behind the bars of an arraignment courtrooms cell. The equity issue that poses is one reason why advocates California Attorneys for Criminal Justice, a statewide association of criminal defense attorneys, has opposed cash bail.

There is an adverse effect because of the appearance of the defendant behind bars, said attorney Stephen Munkelt, executive director of California Attorneys for Criminal Justice. Munkelt said the cells also point to more systemic issues in criminal justice.

CACJ believes the right to liberty has been severely undervalued by the court in the last 40 years (beginning) with the War on Drugs, the decadeslong campaign to stem the illegal drug trade in the U.S., to deleterious effect on Black and brown communities from long prison sentences for non-violent drug offenders to mass incarceration.

Before that, judges understood the right to liberty. People were released pretrial, Munkelt said. Over time, he said, public and political attitudes and media coverage of crime and criminal justice have worked to influence the bench.

It is an ongoing and systemic issue, he said.

Sacramento courts leaders had long argued for a new, modern courthouse to replace the Schaber courthouse, a building for years seen as cramped, obsolete and unsafe. The downtown arraignment cells on Ninth Street and on I Street are among the relics that have long been part of the judicial routine in Sacramento Superior Court.

With new courthouses in Yolo, Placer, Sutter and San Joaquin counties opening in recent years, the arraignment cells inside Sacramentos courtrooms are among the last holdovers from an earlier era. But other local courts, for years, have had their own troubled history.

Yolo County jail inmates as late as 2015 were shepherded in chain gangs from a sheriffs holding facility and through the crowded corridors of the countys century-old courthouse on Court Street. The procession was both a security risk to the court-attending public and an injustice to the inmates facing criminal charges.

Its prejudicial to be chained up in those striped uniforms and led across the street. Its a perp walk, Woodland attorney Steven Sabbadini said in a 2014 interview, as construction was beginning on the new Yolo courthouse. When theyre walking through the halls, its not a good thing for them, for jurors, for witnesses and alleged victims or for family members.

But the cells are also likely a reflection of attitudes on courtroom security and in-courtroom confinement at the time construction of the Patino courtrooms was completed in 1989; and the influence more broadly of county sheriffs officials in the design of court facilities, Munkelt said.

Its a sign of political power and delegation of responsibilities to the sheriff and security staff, Munkelt said. When designers go to construction, the sheriff has basically designed them. The state of the art at the time (that Schaber was built) was to put (inmates) in a box. Im sure thats how it came about.

Sheriffs offices today continue to exert great influence on courthouse security.

Sacramento County sheriffs deputies, as well sheriffs offices as in nearly all of Californias 58 counties marshals in the case of two counties supply courthouses bailiffs and courtroom security, according to the Judicial Council of California, which oversees the states superior courts.

That is as far as the Sheriffs Offices responsibility goes, said Lt. Rodney Grassmann, a Sacramento County sheriffs spokesman. Legislation enacted 20 years ago, the Superior Court Law Enforcement Act of 2002, calls for the presiding judge of each court to contract with the countys sheriff or marshal for the necessary level of law enforcement services subject to the courts available funding.

The courthouse buildings, including the arraignment cells, are the responsibility of the Superior Court, Grassmann said.

But officials at the Judicial Council of California say sheriffs offices play a much greater role, working closely with the court, courthouse designers and the design teams security consultants, to define security operations, procedures, and staffing levels proposed for the new courthouse.

The superior court relies on the sheriff to provide bailiffs and courtroom security, so they have a large amount of influence on how the courts are run and that leads to ongoing problems that concern myself and other criminal defense lawyers, Munkelt said. He says the defense bar should also have some input into how courthouses are designed but says the ability to influence those construction details is extremely limited.

Today at Yolo Superior Courts new Main Street courthouse in Woodland, a basement holding facility holds as many as 140 inmates, with secure elevators to transport those in custody to hearings and trial.

The chain gangs parades through crowded hallways are over. New inmate docks enclosed in plexiglass are now standard equipment in the Woodland courthouses arraignment courts.

The old Yolo courthouse was just not big enough to accommodate a growing county, Yolo County District Attorney Jeff Reisig, said in 2015 upon the opening of the new five-story facility. Its not safe we had chain gangs going up and down the hallways, Reisig said. The new downtown courthouse, he said, was modern, consolidated, high-tech.

At Placer Superior Courts Santucci Justice Center in Roseville, its Department 20 inside the South Placer Adult Correctional Facility opened in 2018. It replaced the tiny, cramped and now-closed Department 13 shoehorned inside Placer County Jail in Auburn. Department 20 features the plexiglass-enclosed arraignment dock standard now in newly built courthouses.

Serious matters are heard in courtrooms. Whether you are here as someone who has been charged with a crime or as a victim or victims relative, legal proceedings need to be done in a dignified, safe and efficient manner, then-Placer Superior Court Presiding Judge Alan V. Pineschi said upon Department 20s debut. Our new Department 20 will provide for that.

Munkelt recalls the construction and opening of Department 20.

Department 20 was built with a large plexiglass box to seat inmates, Munkelt said. When they finished the courtroom and started using it, they said, Its all ready to go.

Only, Munkelt said, attorneys could not communicate through the glass with their clients.

We said, Thats illegal. If the attorney and defendant cant speak to each other.... he said. The defendant had to be out of the box, so we set up a method to speak to them.

Munkelt successfully argued the right of defendants to have face-to-face jail visits with their attorneys before the states Third District Court of Appeal, a decision that has since been used to argue to provide similar access in new California courtrooms.

The appeals court in its 2015 decision, County of Nevada v. Superior Court, ruled that Nevada County Sheriffs Department unconstitutionally barred attorneys and their clients from meeting in jail visiting rooms without glass partitions under the guise of safety and security concerns.

Several inmates wanted to restore the face-to-face contact visits in non-partitioned rooms as had been the practice for years at Nevada Countys Wayne Brown Correctional Facility.

The Nevada Sheriffs Office and other law enforcement organizations across California opposed it on various grounds but appeals judges ruled in favor of defense attorneys and their clients.

Any kind of barrier is a barrier to communication, Munkelt told The Bee. That decision was used in a number of new (courthouse) construction cases. That doesnt mean the problem is solved.

2022 The Sacramento Bee. Visit sacbee.com. Distributed by Tribune Content Agency, LLC.

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'Incredibly prejudicial': Why Sacramento courts have caged cells, and why that'll change - Walla Walla Union-Bulletin

ReportLinker

during the forecast period. Factors such asrising cases of neurological diseases and cancer, growing gene therapy product approvals, and increasing investment in gene therapy related research and development drive the market growth.

New York, Aug. 02, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Gene Therapy Market by Vectors, Indication, Delivery Method, Region - Global Forecast to 2027" - https://www.reportlinker.com/p05843076/?utm_source=GNW However,factors like high cost of gene therapy is restraining the growth of this market.

The cancer segment accounted for the highest growth ratein the gene therapy market, by indication, during the forecast periodIn 2021, cancer segment accounted for the highest growth rate. Growing disease burden of cancer across the globe coupled with rising demand for gene therapies to treat cancer will augment the segmental growth of cancer over the forecast period.

Asia Pacific: The fastest-growing region in the gene therapy marketThe Asia Pacific market is estimated to record the highest CAGR during the forecast period. The high growth rate of this market can be attributed to the improving healthcare expenditure in emerging economies, increasing product launches, and increasing incidence of cancer and neurological diseases.

The primary interviews conducted for this report can be categorized as follows: By Company Type: Tier 1- 32%, Tier 2- 44%, and Tier 3-24% By Designation: C-level (Managers) - 30%, D-level(CXOs, Directors)- 34%, and Others (Executives) - 36% By Region: North America -50%, Europe -32%, Asia-Pacific -10%, Rest of the World -8%

List of Companies Profiled in the Report: Biogen (US) Sarepta Therapeutics (US) Gilead Sciences, Inc. (US) Amgen, Inc. (US) Novartis AG (Switzerland) Orchard Therapeutics Plc (UK) Spark Therapeutics, Inc. (A Part Of ?F. Hoffmann-La Roche) (US) AGC Biologics (US) Anges, Inc. (Japan) Bluebird Bio, Inc. (US) Jazz Pharmaceuticals Plc (Ireland) Dynavax Technologies (US) Human Stem Cells Institute (Russia) SibionoGenetech Co., Ltd. (China) Shanghai Sunway Biotech Co., Ltd. (China) Uniqure N.V. (Netherland) Gensight Biologics S.A. (France) Celgene Corporation (A Bristol-Myers Squibb Company) (US) Cellectis (France) Sangamo Therapeutics (US) Mustang Bio (US) AGTC (Applied Genetic Technologies Corporation) (US) Poseida Therapeutics, Inc. (US)

Research Coverage:This report provides a detailed picture of the global gene therapy market.It aims at estimating the size and future growth potential of the market across different segments such as vectors, indication, delivery method, and region.

The report also includes an in-depth competitive analysis of the key market players along with their company profiles recent developments and key market strategies.

Key Benefits of Buying the Report:The report will help market leaders/new entrants by providing them with the closest approximations of the revenue numbers for the overall gene therapy market and its subsegments.It will also help stakeholders better understand the competitive landscape and gain more insights to better position their business and make suitable go-to-market strategies. This report will enable stakeholders to understand the markets pulse and provide them with information on the key market drivers, challenges,trends,and opportunities.Read the full report: https://www.reportlinker.com/p05843076/?utm_source=GNW

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The global gene therapy market is valued at an estimated USD 7.3 billion in 2022 and is projected to reach USD 17.2 billion by 2027, at a CAGR of...