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Liu Y, Li G, Yang G, et al. Increasing the targeting scope and efficiency of base editing with Proxy-BE strategy. FEBS Lett. 2019;594(8):1319-1328doi: 10.1002/1873-3468.13719.
Liu, Y., Li, G., Yang, G., Gu, H., Huang, S., Yu, W., Qin, G., Liu, X., Zhou, F., Huang, X., & Wei, Y. (2020). Increasing the targeting scope and efficiency of base editing with Proxy-BE strategy. FEBS letters, 594(8), 1319-1328. https://doi.org/10.1002/1873-3468.13719
Liu, Yin, et al. "Increasing the targeting scope and efficiency of base editing with Proxy-BE strategy." FEBS letters vol. 594,8 (2020): 1319-1328. doi: https://doi.org/10.1002/1873-3468.13719
Liu Y, Li G, Yang G, Gu H, Huang S, Yu W, Qin G, Liu X, Zhou F, Huang X, Wei Y. Increasing the targeting scope and efficiency of base editing with Proxy-BE strategy. FEBS Lett. 2020 Apr;594(8):1319-1328. doi: 10.1002/1873-3468.13719. Epub 2019 Dec 29. PMID: 31837228.
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FEBS Lett. 2020 Apr;594(8):1319-1328. doi: 10.1002/1873-3468.13719. Epub 2019 Dec 29.

Increasing the targeting scope and efficiency of base editing with Proxy-BE strategy.

FEBS letters

Yin Liu, Guanglei Li, Guang Yang, Huifeng Gu, Shisheng Huang, Wenxia Yu, Guizhen Qin, Xinyi Liu, Fuling Zhou, Xingxu Huang, Yongchang Wei

Affiliations

  1. Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, China.
  2. School of Life Science and Technology, ShanghaiTech University, China.
  3. Department of Gastroenterology, Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, China.
  4. Department of Hematology, Zhongnan Hospital of Wuhan University, China.

PMID: 31837228 DOI: 10.1002/1873-3468.13719

Abstract

Base editors (BEs) are widely used in precise gene editing due to their simplicity and versatility. However, their efficiencies are hindered by various obstacles. Considering the chromatin microenvironment as a possible obstacle, here, we demonstrate a further development of the proxy-clustered regularly interspaced short palindromic repeats strategy, termed Proxy-BE, to increase gene editing efficiency. Specifically, a nuclease-dead Cas9 (dCas9) was bound to the sequence about 20-30 base pair away from the target site, potentially improving access to the DNA and, thus, providing a better editing microenvironment for base editors. Our findings confirm that nuclease-dead Streptococcus pyogenes Cas9 can assist the base editors SaKKH-BE3 and dCpf1-BE to double their canonical base editing efficiency. This work provides a new approach to enhance base editing, extending its scope for biological research and gene therapy.

© 2019 Federation of European Biochemical Societies.

Keywords: CRISPR; Cas9; SaKKH-BE3; base editing; dCpf1-BE; gene editing

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