Identification of non-toxic AAV capsid variants with enhanced deep retinal transduction and extended distribution following subretinal delivery - PubMed
6 hours ago
- #retinal gene therapy
- #AAV capsid engineering
- #phage display
- Subretinal injection is the standard method for retinal gene delivery, but wild-type AAV2 vectors are limited by sequestration at the retinal pigment epithelium (RPE).
- An in vitro phage display strategy was used to identify novel AAV capsids with enhanced retinal transduction efficiency.
- Systematic screening under low multiplicity of infection conditions identified variants with superior transduction potencies.
- The lead engineered capsid demonstrated a non-toxic profile and efficiently transduced the inner nuclear layer (INL), typically inaccessible to conventional AAV2 vectors.
- The study suggests a next-generation AAV platform for deep retinal transduction, beneficial for gene therapies requiring broad retinal coverage.