한빛사 논문
Ha Rim Shin1,2,†, Ji-Eun See1,2,†, Jiyeon Kweon1,2, Heon Seok Kim3,4, Gi-Jun Sung1,2,
Sojung Park5,6, An-Hee Jang1,2, Gayoung Jang1,2, Kyung-Chul Choi1,2,7, Inki Kim5,6,
Jin-Soo Kim3,4 and Yongsub Kim1,2,*
1Department of Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,
2Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,
3Center for Genome Engineering, Institute for Basic Science, Daejeon, Republic of Korea,
4Department of Chemistry, Seoul National University, Seoul, Republic
of Korea,
5Convergence Medicine Research Center (CREDIT)/Biomedical Research Center, Asan Institute for Life Sciences, Seoul, Republic of Korea,
6Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea and
7Department of Pharmacology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Republic of Korea
*To whom correspondence should be addressed.
†The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.
Present address: Heon Seok Kim, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Abstract
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.
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