functional-assessment-brca1-variants-using-crispr-mediated-base

Functional Assessment of <em>BRCA1</em> variants using CRISPR-Mediated Base Editors

Recent studies have investigated the risks associated with BRCA1 gene mutations using various functional assessment methods such as fluorescent reporter ...

University of Ulsan College of Medicine

CRISPR-based base editors (BEs) are widely used to induce nucleotide substitutions in living cells and organisms without causing the damaging DNA double-strand breaks and DNA donor templates. Cytosine BEs that induce C:G to T:A conversion and adenine BEs that induce A:T to G:C conversion have been developed. Various attempts have been made to increase the efficiency of both BEs; however, their activities need to be improved for further applications. Here, we describe a fluorescent reporter-based drug screening platform to identify novel chemicals with the goal of improving adenine base editing efficiency. The reporter system revealed that histone deacetylase inhibitors, particularly romidepsin, enhanced base editing efficiencies by up to 4.9-fold by increasing the expression levels of proteins and target accessibility. The results support the use of romidepsin as a viable option to improve base editing efficiency in biomedical research and therapeutic genome engineering.

Gayoung Jang

Department of Biomedical Sciences,
Asan Medical Institute of Convergence Science and Technology,
Asan Medical Center,
Stem Cell Immunomodulation Research Center,
Department of Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center

University of Ulsan College of Medicine

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors