StemCell Therapy

University of Minnesota Twin Cities researchers in the Department of Chemistry have created a new polymer to deliver DNA and RNA-based therapies for diseases. For the first time in the industry, the researchers were able to see exactly how polymers interact with human cells when delivering medicines into the body. This discovery opens the door for more widespread use of polymers in applications like gene therapy and vaccine development.

The research is published in the Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed multidisciplinary scientific journal.

Gene therapy involves altering the genes inside the bodys cells to treat or cure diseases. It requires a carrier that packages the DNA to deliver it into the celloftentimes, a virus is used as a carrier. Packaging of nucleic acids is also used in vaccines, such as the recently developed messenger RNA (mRNA) COVID-19 vaccine, which is enclosed in a lipid.

The research team is led by chemistry professor Theresa Reineke and associate professor Renee Frontiera. Reinekes lab synthesizes polymers, which are long-chain molecules that make up plastics, to use for packaging the nucleic acids instead.

Its kind of like ordering something from Amazon, and its shipped in a box, Reineke explained. Things get broken if theyre not delivered in a package. Thats basically what were doing here but on a nano-level. Were taking these really sensitive RNA and DNA cargo that are susceptible to enzymatic degradation, that wont get to their target unless you have something to protect them.

The researchers designed the copolymer using quinine, a naturally occurring substance used in tonic water, and 2-hydroxyethyl acrylate (HEA), which makes the material soluble and is used in a variety of personal care and medical materials. Because quinine is fluorescent, the research team was able to track the DNA package throughout the body and into the cells using Raman spectroscopy, a chemical imaging technique.

Weve discovered a new packaging tool with this natural product thats important for all of these high-flying, important fields like gene therapy and vaccines, said Reineke, who is also a Distinguished McKnight University Professor. And, it works in a variety of cell-types. On top of that, its got all of these cool featuresits fluorescent, we can track it, its Raman active, and that allowed us to understand a lot of fundamentals about these packaging systems that were impossible to probe before we incorporated this natural product.

Polymer-based drug delivery is significantly cheaper than using viruses, especially for gene therapy, which can cost up to $2 million for a single injection. However, the main barrier preventing widespread polymer use was that scientists didnt know a lot about how the polymer package actually interacts with cells in the body.

This research helps clear up that uncertainty. Frontieras lab specializes in chemical imaging. Using Raman spectroscopy, they discovered that a cells own proteins play a key role in unpacking the nucleic acid cargo once the polymer carrier enters the cell.

Its very satisfying to know how this is actually happening, what the process of delivery is, and to actually see that in real-time, Frontiera said. A key point is that these polymers also work very well. For all the beneficial attributes, theyre also incredibly effective at getting the payload into cells, and we were able to tell why, which doesnt always happen in this field.

Reineke and Frontiera have been collaborating since 2013. Reinekes lab has patented the quinine polymers, and the researchers hope that a company might license this technology in the future. The College of Science and Engineering team also collaborated with University of Minnesota Medical School Distinguished McKnight University Professor Jakub Tolar to test the effectiveness of the polymer carriers in relevant cell types.

Other members of the research team include chemistry researchers Craig Van Bruggen (Ph.D. student) and David Punihaole (postdoctoral associate), chemical engineering and materials science student Andrew Schmitz, and genetics Ph.D. student Allison Keith. This research was funded by the National Science Foundation and the National Institutes of Health.

Read the full research paper entitled Quinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism on the PNAS website.

Read more from the original source:
Researchers discover new way to deliver DNA-based therapies for diseases - UMN News

This entry was posted on December 22, 2020 at 4:53 pm and is filed under Gene therapy. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |