Efficient DNA base editing via an optimized DYW-like deaminase

CRISPR-based cytosine base editors enable precise genome editing without inducing double-stranded DNA breaks, yet traditionally depend on a limited selection of deaminases from the APOBEC/AID or TadA families. Here, we introduce SsCBE, a novel CRISPR-based cytosine base editor utilizing SsdAtox, a DYW-like deaminase derived from the toxin of Pseudomonas syringae. Strategic engineering of SsdAtox has led to remarkable improvements in the base editing efficiency (by up to 8.4-fold) and specificity for SsCBE, while concurrently reducing cytotoxicity. Exhibiting exceptional versatility, SsCBE was delivered and efficiently applied using diverse delivery methods, including the engineered virus-like particles (eVLPs). Its application has enabled targeted cytosine base editing in mouse zygotes and pioneering edits in mitochondrial DNA. The advent of SsCBE marks a significant advancement in the CRISPR toolkit, providing a versatile tool for advanced research and therapeutic strategies.

• Publication year

  2024

• Venue

  bioRxiv

• Publication date

  2024-05-16

• Fields of study

  Biology, Chemistry, Engineering

• Identifiers
  DOI 10.1101/2024.05.15.594452
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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