CRISPR-Cas9 has revolutionize medicine as an emerging tool to treat a multitudeofhuman genetic diseases, such as Transfusion Dependent β-thalassemia and Sickle Cell Disease. Desipite these advances, development of Cas9 variants with increased fidelity are still plagued with off-target effects, DNA-damage toxicity, or stringent PAM requirements. To design variants with improved DNA cleavages, the catalytic mechanism behind target and non-target cleavageneeds to be betterunderstood. In our work, the non-target strand cleavage of SpyCas9 is studied using machine-learning-assisted QM/MM free energy simulations.

Exploring the non-target strand cleavage of SpyCas9 with machine-learning-assisted QM/MM free energy simulations

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.