Chemically-inducible CRISPR/Cas9 circuits for ultra-high dynamic range gene perturbation.

ABSTRACT: CRISPR/Cas9 technologies provide unique capabilities for modeling disease and understanding gene-to-phenotype connections. In cultured cells, chemical-mediated control of Cas9 activity can limit off-target effects and enable mechanistic study of essential genes. However, widely-used Tet-On systems often show leaky Cas9 expression, leading to unintended edits, as well as weak activity upon induction. Leakiness can be problematic in the context of Cas9 nuclease activity, which may result in cumulative DNA damage and degradation of the target cell genome over time. To overcome these deficiencies, we have established transgenic platforms that minimize Cas9 functionality in the OFF-state along with maximized and uncompromised ON-state gene editing efficiency. By combining conditional destabiliz

SUBMITTER: Srinivasan R 

PROVIDER: S-EPMC12804943 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature