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04/21/15 11:33 AM

#190250 RE: DewDiligence #190244

AGTC, AAVL > interesting...comparing both AMD programs...

AAVL's AAV is delivered subretinal, AGTC/Genzyme is/was delivered intravitreal. Also, since Genzyme released restrictions, AGTC's AMD program is back on the table according to their presentation. Could we see AMD studies based on intravitreal delivery of 7m8 (or similar) vector? An intravitreal injection is less risky and would be much preferred vs. subretinal...would it not?

Found this...

Antibody Neutralization Poses a Barrier to Intravitreal Adeno-Associated Viral Vector Gene Delivery to Non-Human Primates

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393652/

Analysis showed that intravitreal administration resulted in an increase in anti-AAV antibodies regardless of the capsid serotype, transgene, or dosage of virus injected. For monkeys injected with wild-type AAV2 and/or an AAV2 mutant, the variable that most significantly affected the production of anti-AAV2 antibodies was the amount of virus delivered. In addition, post-injection antibody titers were highest against the serotype administered, but the antibodies were also cross-reactive against other AAV serotypes. Furthermore, neutralizing antibody levels in serum correlated with those in vitreal fluid, demonstrating both that this route of administration exposes AAV capsid epitopes to the adaptive immune system and that serum measurements are predictive of vitreous fluid NAB titers. Moreover, the presence of pre-existing neutralizing antibody titers in the serum of monkeys correlated strongly (R=0.76) with weak, decaying, or no transgene expression following intravitreal administration of AAV.