Cochlear AAV Inflammation 2025
Acta Oto-Laryngologica 2025: serotype-dependent macrophage activation in AAV-mediated cochlear gene therapy.
Different AAV serotypes trigger different inflammatory profiles in the cochlea. Not just different antibody responses. Different innate immune activation. Macrophages, cytokines, the whole local inflammatory cascade. Promoter choice also affects immunogenicity, which adds another variable to vector design.
This is a gap in our current immune response model. The STRC Anti-AAV Immune Response Model covers NAb kinetics and seroprevalence (the “can we get the vector in” question). But it doesn’t cover what happens after the vector arrives. Local innate immune response in the cochlea could reduce transduction efficiency or, worse, damage hair cells that were fine before treatment.
The cochlea is an immune-privileged site, but not immune-silent. The blood-labyrinth barrier provides some protection, but AAV delivered directly through the round window membrane bypasses that barrier. You’re putting foreign protein directly into a space that doesn’t normally see it.
Capsid selection and promoter choice aren’t just about transduction efficiency. They’re about not triggering an inflammatory response that undermines the therapy. Need to add this dimension to the immune hypothesis.
Connections
- STRC Gene Therapy — inflammation as vector design constraint
- STRC Anti-AAV Immune Response Model — gap: innate immune response not covered
- STRC AAV Vector Design — capsid and promoter affect immunogenicity
- New AAV Capsids 2025 Cochlear — capsid choice has inflammatory implications
- AAV Capsid Database — serotype-specific immune data