Chronic In Vivo CRISPR-Cas Genome Editing: Challenges, Long-Term Safety, and Outlook.

ABSTRACT: CRISPR/Cas systems have transformed molecular medicine, yet the field still lacks principled guidance on when transient editing suffices versus when sustained exposure through in vivo viral delivery is necessary and how to keep prolonged exposure safe. Notably, EDIT-101 was designed for a permanent edit in post-mitotic photoreceptors with lifelong Cas9 persistence. This review addresses this gap by defining the biological and therapeutic conditions that drive benefit from extended Cas activity while minimizing risk. We will (i) examine relationships between expression window and efficacy across Cas9/Cas12/Cas13 modalities, (ii) identify genome-wide off-target liabilities alongside orthogonal assays, and (iii) discuss controllable, self-limiting, and recallable editor platforms. By separati

SUBMITTER: Bao C 

PROVIDER: S-EPMC12838982 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature