Retinal Epithelial Neutralization Assay Optimizes AAV Serotype Selection for Ocular Gene Therapy.

ABSTRACT: Adeno-associated virus (AAV) vectors face a critical translational challenge in ocular gene therapy due to pre-existing neutralizing antibodies (NAbs) whose seroprevalence limits patient eligibility. Standard NAb detection using non-ocular cell models (Human Embryonic Kidney 293T) may inadequately predict retinal transduction inhibition due to cell type-related variations in receptor usage and immunogenicity. This study established parallel NAb detection platforms utilizing human retinal pigment epithelial (ARPE-19) cells and standard 293T cells to systematically evaluate clinical serum samples against ophthalmologically relevant AAV serotypes (2, 5, 8, 9) via luciferase reporter-based transduction inhibition assays. Comparative analysis demonstrated ARPE-19 exhibited 42-48% higher NAb tit

SUBMITTER: Li Y 

PROVIDER: S-EPMC12300778 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature