Efficient C-to-G Base Editing with Improved Target Compatibility Using Engineered Deaminase-nCas9 Fusions.

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  • Author(s): Chen S;Chen S; Liu Z; Liu Z; Lai L; Lai L; Lai L; Lai L; Lai L; Li Z; Li Z
  • Source:
    The CRISPR journal [CRISPR J] 2022 Jun; Vol. 5 (3), pp. 389-396. Date of Electronic Publication: 2022 Mar 02.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 101738191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2573-1602 (Electronic) Linking ISSN: 25731599 NLM ISO Abbreviation: CRISPR J Subsets: MEDLINE
    • Publication Information:
      Original Publication: [New Rochelle, NY] : Mary Ann Liebert, Inc., [2018]-
    • Subject Terms:
      CRISPR-Cas Systems*/genetics ; Gene Editing*; Adenine ; Animals ; Cytosine ; Genome ; Mice
    • Abstract:
      CRISPR-guided DNA base editors (BEs) are potent genome editing tools in biotechnology and medicine. However, conventional cytosine and adenine BEs can only induce base transitions (C-to-T and A-to-G) and cannot induce base transversions. Recently, several C-to-G base editors (CGBEs) were generated and applied in human cells. By comparing them, we found that engineered deaminases rather than additional base excision repair proteins significantly improved the C-to-G efficiency. In addition, significant increase in C-to-G transversions in the GC context were determined by using rationally engineered eAID deaminase. The genome-targeting scope of CGBEs were further expanded by using SpRY Cas9 variant, which then successfully induced stop codon (TAC to TAG) to disrupt Tyr gene in mouse embryos. Taken together, these new CGBEs with engineered deaminase-nCas9 fusions broaden the BE toolsets for efficient gene modification and therapeutic applications.
    • Accession Number:
      8J337D1HZY (Cytosine)
      JAC85A2161 (Adenine)
    • Publication Date:
      Date Created: 20220303 Date Completed: 20220614 Latest Revision: 20220617
    • Publication Date:
      20240105
    • Accession Number:
      10.1089/crispr.2021.0124
    • Accession Number:
      35238619