Molecular basis of target RNA cleavage by Cas13

Joe K C Lam1, Summerloretta S K Leung1, Jason Ying Ki Li1

  • 1School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Nature Communications
|April 8, 2026
PubMed

Insights

CRISPR-Cas13 enzymes precisely cleave RNA targets in vivo. This research elucidates Cas13 cleavage mechanisms and develops RNA Segment Editing (RSE) for precise RNA repair and engineering.

Area of Science:

  • Molecular Biology
  • Biotechnology
  • Genetics

Background:

  • RNA-targeting CRISPR-Cas13 enzymes offer potent RNA knockdown capabilities.
  • However, their in vivo RNA cleavage mechanisms are not fully understood.
  • Understanding these mechanisms is crucial for advancing RNA-based technologies.

Purpose of the Study:

  • To elucidate the precise in vivo RNA cleavage sites of CRISPR-Cas13 enzymes.
  • To engineer Cas13 subtypes for improved cleavage precision.
  • To develop a novel RNA repair method based on precise cleavage.

Main Methods:

  • Combined in vitro and in vivo experimental approaches.
  • Characterization of cleavage site specificity for Cas13 subtypes (e.g., Cas13b, Cas13bt).
  • Rational engineering of Cas13 enzymes to enhance cleavage accuracy.

Main Results:

  • Identified predominant cleavage positions for specific Cas13 subtypes.
  • Demonstrated that rational engineering significantly improves Cas13 cleavage precision.
  • Developed RNA Segment Editing (RSE) for targeted RNA cleavage and repair.

Conclusions:

  • Cas13 subtypes exhibit specific in vivo RNA cleavage patterns.
  • Engineered Cas13 variants offer enhanced precision for RNA targeting.
  • RNA Segment Editing (RSE) presents a promising tool for precision RNA engineering in therapeutics and research.

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