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Improving adenine and dual base editors through introduction of TadA-8e and Rad51DBD.
Xue, Niannian; Liu, Xu; Zhang, Dan; Wu, Youming; Zhong, Yi; Wang, Jinxin; Fan, Wenjing; Jiang, Haixia; Zhu, Biyun; Ge, Xiyu; Gonzalez, Rachel V L; Chen, Liang; Zhang, Shun; She, Peilu; Zhong, Zhilin; Sun, Jianjian; Chen, Xi; Wang, Liren; Gu, Zhimin; Zhu, Ping; Liu, Mingyao; Li, Dali; Zhong, Tao P; Zhang, Xiaohui.
Afiliação
  • Xue N; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Liu X; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Zhang D; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Wu Y; Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Zhong Y; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Wang J; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Fan W; Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Jiang H; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Zhu B; Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Ge X; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Gonzalez RVL; School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  • Chen L; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Zhang S; Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • She P; Department of Physiology and Cellular Biophysics, Columbia University, Manhattan, NY, USA.
  • Zhong Z; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Sun J; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Chen X; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Wang L; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Gu Z; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Zhu P; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Liu M; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Li D; BRL Medicine, Inc., Shanghai, China.
  • Zhong TP; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Zhang X; Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Nat Commun ; 14(1): 1224, 2023 03 03.
Article em En | MEDLINE | ID: mdl-36869044
ABSTRACT
Base editors, including dual base editors, are innovative techniques for efficient base conversions in genomic DNA. However, the low efficiency of A-to-G base conversion at positions proximal to the protospacer adjacent motif (PAM) and the A/C simultaneous conversion of the dual base editor hinder their broad applications. In this study, through fusion of ABE8e with Rad51 DNA-binding domain, we generate a hyperactive ABE (hyABE) which offers improved A-to-G editing efficiency at the region (A10-A15) proximal to the PAM, with 1.2- to 7-fold improvement compared to ABE8e. Similarly, we develop optimized dual base editors (eA&C-BEmax and hyA&C-BEmax) with markedly improved simultaneous A/C conversion efficiency (1.2-fold and 1.5-fold improvement, respectively) compared to A&C-BEmax in human cells. Moreover, these optimized base editors catalyze efficiently nucleotide conversions in zebrafish embryos to mirror human syndrome or in human cells to potentially treat genetic diseases, indicating their great potential in broad applications for disease modeling and gene therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Adenina Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Adenina Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article