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

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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.
Author(s)
김진수신하림시지은권지연김헌석성기준박소정장안희장가영최경철김인기김용섭
Issued Date
2021
Type
Article
Keyword
CRISPR-Casgenome engineeringbase editingHDAC inhibitor
DOI
10.1093/nar/gkab052
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7530
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7913676&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Small-molecule%20inhibitors%20of%20histone%20deacetylase%20improve%20CRISPR-based%20adenine%20base%20editing&offset=0&pcAvailability=true
Publisher
NUCLEIC ACIDS RESEARCH
Location
영국
Language
영어
ISSN
0305-1048
Citation Volume
49
Citation Number
4
Citation Start Page
2390
Citation End Page
2399
Appears in Collections:
Medicine > Medicine
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