| dc.description.abstract | The CRISPR/Cas9 system has revolutionized gene editing by offering a simple,
cost-effective, and versatile tool for therapeutic and clinical applications.
However, absolute precision remains a challenge due to off-target effects and
genotoxicity. To address this issue, a novel regulatory strategy for CRISPR/Cas9
is presented, incorporating a controllable anti-CRISPR protein, AcrIIA4, fused
with a destabilization domain. This fusion protein inhibits Cas9 activity in the
presence of the small molecule trimethoprim. A primary switch system was
developed by integrating the AcrIIA4-destabilization domain complex into the
Cas9 sequence within a single plasmid vector. This regulation system effectively
modulates Cas9 activity, thereby enhancing the precision of gene editing. The
approach lays the groundwork for more accurate and controllable gene therapy
methods, reducing the risk of off-target alterations and improving safety profiles
in clinical applications. The successful construction and validation of this
regulatory mechanism based on anti-CRISPR protein represent a significant
advancement in the field, paving the way for the development of next-generation
gene editing technologies with enhanced specificity and reduced genotoxicity. | en_US |
