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Small-molecule inhibitors of histone deacetylase improve CRISPR-based adenine base editing

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Title
Small-molecule inhibitors of histone deacetylase improve CRISPR-based adenine base editing
Author(s)
Shin, Ha Rim; See, Ji-Eun; Kweon, Jiyeon; Heon Seok Kim; Sung, Gi-Jun; Park, Sojung; Jang, An-Hee; Jang, Gayoung; Choi, Kyung-Chul; Kim, Inki; Jin-Soo Kim; Kim, Yongsub
Publication Date
2021-02
Journal
Nucleic acids research, v.49, no.4, pp.2390 - 2399
Publisher
NLM (Medline)
Abstract
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.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.
URI
https://pr.ibs.re.kr/handle/8788114/9501
DOI
10.1093/nar/gkab052
ISSN
0305-1048
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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