Adeno-associated virus serotype 2 capsid variants for improved liver-directed gene therapy.

ABSTRACT:

Background and aims

Current liver-directed gene therapies look for adeno-associated virus (AAV) vectors with improved efficacy. With this background, capsid engineering is explored. Whereas shuffled capsid library screenings have resulted in potent liver targeting variants with one first vector in human clinical trials, modifying natural serotypes by peptide insertion has so far been less successful. Here, we now report on two capsid variants, MLIV.K and MLIV.A, both derived from a high-throughput in vivo AAV peptide display selection screen in mice.

Approach and results

The variants transduce primary murine and human hepatocytes at comparable efficiencies, a valuable feature in clinical development, and show significantly improved liver transduction efficacy, thereby allowi

SUBMITTER: Meumann N 

PROVIDER: S-EPMC9936986 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature