AAV Kills Dividing Cells by Depleting PARP1 and Other DNA Damage Response Proteins.

ABSTRACT: Recombinant adeno-associated virus (rAAV) is a replication-defective viral vector used in hundreds of human gene therapy trials, resulting in five FDA-approved therapies. Despite this success, rAAV-based gene therapies suffer from dose-limiting toxicities, resulting in several severe adverse reactions, including death. Previously, we discovered that rAAV rapidly kills mouse NPCs in vitro and in vivo. This vector contains a minimal genome comprised of 145-base pair inverted terminal repeats (ITRs) with a T-shaped hairpin structure that appears to be necessary and sufficient for this toxicity. However, the mechanism for AAV ITR toxicity is not known, and there have been few attempts to engineer ITRs to attenuate rAAV toxicity. In the current study, we explore the molecular mechanisms that dr

SUBMITTER: Friese S 

PROVIDER: S-EPMC12632961 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature