Cell-penetrating peptide-grafted AAV2 capsids for improved retinal delivery via intravitreal injection.

ABSTRACT: Recombinant adeno-associated virus (rAAV) is a leading vector for retinal gene therapy due to its favorable safety profile demonstrated by the FDA-approved Luxturna for Leber congenital amaurosis. However, challenges with low transduction efficiency and immunogenicity, coupled with the invasiveness of subretinal injections, have driven efforts to engineer AAV capsids for minimally invasive intravitreal delivery. Intravitreal injections face the barrier of the inner limiting membrane (ILM), particularly with AAV2-based vectors. In this study, we displayed cell-penetrating peptides (CPPs) on AAV2 capsids to enhance retinal cell transduction via intravitreal injection. Through in vivo capsid screening, we identified AAV2.CPP1, which showed significantly improved pan-retinal expression

SUBMITTER: Wang JH 

PROVIDER: S-EPMC11872077 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature