Ancestral library identifies conserved reprogrammable liver motif on AAV capsid.

ABSTRACT: Gene therapy is emerging as a modality in 21st-century medicine. Adeno-associated viral (AAV) gene transfer is a leading technology to achieve efficient and durable expression of a therapeutic transgene. However, the structural complexity of the capsid has constrained efforts to engineer the particle toward improved clinical safety and efficacy. Here, we generate a curated library of barcoded AAVs with mutations across a variety of functionally relevant motifs. We then screen this library in vitro and in vivo in mice and nonhuman primates, enabling a broad, multiparametric assessment of every vector within the library. Among the results, we note a single residue that modulates liver transduction across all interrogated models while preserving transduction in heart and skeletal muscles. Mor

SUBMITTER: Zinn E 

PROVIDER: S-EPMC9729830 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature