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Small-molecule inhibitors of histone deacetylase improve CRISPR-based adenine base editing.
Shin, Ha Rim; See, Ji-Eun; Kweon, Jiyeon; Kim, Heon Seok; Sung, Gi-Jun; Park, Sojung; Jang, An-Hee; Jang, Gayoung; Choi, Kyung-Chul; Kim, Inki; Kim, Jin-Soo; Kim, Yongsub.
Afiliación
  • Shin HR; Department of Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • See JE; Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Kweon J; Department of Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Kim HS; Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Sung GJ; Department of Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Park S; Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Jang AH; Center for Genome Engineering, Institute for Basic Science, Daejeon, Republic of Korea.
  • Jang G; Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
  • Choi KC; Department of Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Kim I; Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Kim JS; Convergence Medicine Research Center (CREDIT)/Biomedical Research Center, Asan Institute for Life Sciences, Seoul, Republic of Korea.
  • Kim Y; Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Nucleic Acids Res ; 49(4): 2390-2399, 2021 02 26.
Article en En | MEDLINE | ID: mdl-33544854
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenina / Inhibidores de Histona Desacetilasas / Sistemas CRISPR-Cas / Edición Génica Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenina / Inhibidores de Histona Desacetilasas / Sistemas CRISPR-Cas / Edición Génica Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido