期刊
NUCLEIC ACIDS RESEARCH
卷 49, 期 4, 页码 2390-2399出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab052
关键词
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资金
- National Research Foundation of Korea [2017M3A9B4062419, 2017M3A9B406 2419, 2020R1F1A1075508, 2018R1A5A2020732]
- National Research Foundation of Korea [2020R1F1A1075508, 2017M3A9B4062419] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
CRISPR-based base editors are widely used for nucleotide substitutions without causing DNA breaks. Efforts are being made to improve the efficiency of both cytosine and adenine base editors. A study has identified histone deacetylase inhibitors, particularly romidepsin, as a potential option to enhance base editing efficiency.
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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