Systemic administration of novel engineered AAV capsids facilitates enhanced transgene expression in the macaque CNS.

ABSTRACT:

Background

Adeno-associated virus (AAV) vectors are a promising vehicle for noninvasive gene delivery to the central nervous system via intravenous infusion. However, naturally occurring serotypes have a limited ability to transduce the brain, and translating engineered capsids from mice to nonhuman primates has proved challenging.

Methods

In this study, we use an mRNA-based directed-evolution strategy in multiple strains of mice as well as a de novo selection in cynomolgus macaques to identify families of engineered vectors with increased potency in the brain and decreased tropism for the liver.

Findings

We compare the transgene expression capabilities of several engineered vectors and show that while some of our novel macaque-derived variants significantly outperfor

SUBMITTER: Stanton AC 

PROVIDER: S-EPMC9840684 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature