Casey Maguire, PhD, on Combining Viral-Like Particles and AAV

“AAV is basically the lead in vivo gene therapy delivery vehicle right now. But it has some challenges such as immunogenicity, and some toxicity at higher doses, and viral-like particles, on the other side, have more favorable, lower immunogenicity, but they're not that great at getting cargo to the nucleus. So, we've combined these two systems together to make an enveloped AAV.”

Extracellular vesicle-associated adeno-associated virus vectors (EV-AAV) may offer a safer way to deliver AAV gene therapies. The technology combines elements of AAV and viral-like particles (VLPs) to create a product designed to be more efficacious than VLPs alone and safer than AAVs alone.

Casey Maguire, PhD, associate professor of neurology at Harvard Medical School and associate investigator of neurology at Massachusetts General Hospital, presented research on EV-AAVs from his lab at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland.

CGTLive® spoke with Maguire to learn more about EV-AAVs and how the next generation technology might help address challenges with current AAV vectors, including toxicity. He overviewed his lab’s research in improving these EV-AAVs and the advantages that the technology may offer over traditional AAVs. He also mentioned a poster by Miguel Santoscoy, PhD, a postdoc researcher in his lab, that focused on engineering the lipid part of the system and favorably shifting the yield of fully enveloped AAVs instead of free AAVs during the manufacturing.

Click here to read more coverage of the 2024 ASGCT Annual Meeting.

REFERENCE

Cheng M, de la Cruz D, Ng C, et al. New Biological Insights into Extracellular Vesicle Associated AAV Help Improve Vector Yield and Provides Rational for Intraluminal AAV Packing. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract 221.