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AAVAnc80-3'hOTOF is a recombinant adeno-associated virus (AAV) vector that serves as the 3' (C-terminal) component of **AK-OTOF** (also known as LY3884961), a dual-vector gene therapy developed by **Akouos** (a subsidiary of Eli Lilly). It is specifically designed to treat **otoferlin gene-mediated hearing loss**, a form of sensorineural deafness caused by mutations in the *OTOF* gene. Because the *OTOF* cDNA sequence (~6 kb) exceeds the standard packaging capacity of a single AAV vector (~4.7 kb), Akouos utilizes a split-gene strategy. AAVAnc80-3'hOTOF carries the 3' segment of the human *OTOF* gene, while a complementary 5' vector carries the remaining sequence. Both vectors utilize the synthetic **AAV-Anc80** capsid, which is engineered for high-efficiency transduction of cochlear inner hair cells. Following a single intracochlear administration of the dual-vector mixture, the two fragments undergo protein trans-splicing or DNA recombination to express full-length, functional otoferlin protein, thereby restoring auditory neurotransmission.
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