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

Ha Rim Shin, Ji Eun See, Jiyeon Kweon, Heon Seok Kim, Gi Jun Sung, Sojung Park, An Hee Jang, Gayoung Jang, Kyung Chul Choi, Inki Kim, Jin Soo Kim, Yongsub Kim

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)2390-2399
Number of pages10
JournalNucleic Acids Research
Volume49
Issue number4
DOIs
StatePublished - 26 Feb 2021

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