Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.

ABSTRACT: Recombinant adeno-associated virus (rAAV) vectors stand out as highly promising for in vivo gene transfer, particularly in targeting the skeletal muscle for treating muscular genetic diseases or secreting therapeutic factors. Despite the simplicity and efficacy of the established intramuscular (IM) route, it has been often associated with an immune-induced rapid loss of transgene expression, in particular in large animal models, and generally considered irreversible as a consequence of a cytotoxic elimination of transduced cells. Here, we report in a non-human primate model that transgene expression loss after IM delivery of an rAAV1 expressing an immunogenic protein is only transient, with the re-expression of the transgene lasting up to 5 years post-injection. We show that the rec

SUBMITTER: Journou M 

PROVIDER: S-EPMC11914520 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature