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Repurposing Cas13's collateral cleavage activity to mitigate host cell dominance in interspecies chimera formation

Jiaowei Wang1, Liangxue Lai1

  • 1CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.

Developmental Cell
|March 12, 2026
PubMed

Insights

Researchers used Cas13 to reduce host cell competition, improving human cell integration in mice. This advance enhances the potential for creating human-animal chimeras for scientific research.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Biotechnology

Background:

  • Interspecies chimera generation is crucial for studying human development and disease.
  • A major challenge is the limited contribution of human cells within host embryos.
  • Overcoming host cell competitiveness is key to improving human cell integration.

Purpose of the Study:

  • To develop a novel method for increasing human cell contribution in interspecies chimeras.
  • To address the obstacle of insufficient human cell integration in host embryos.
  • To leverage CRISPR-Cas13 technology for enhancing xenogeneic cell engraftment.

Main Methods:

  • Utilized the RNA collateral cleavage activity of Cas13.
  • Engineered Cas13 to target and reduce the expression of key host cell genes.
  • Introduced Cas13 system into human cells for co-culture with host mouse embryos.
  • Assessed the integration ratio and contribution of human cells in resulting chimeras.

Main Results:

  • Successfully diminished the competitive advantage of host mouse cells.
  • Significantly increased the integration ratio of human cells in host mice.
  • Achieved up to 1% contribution of human cells in chimeric mice.
  • Demonstrated the efficacy of Cas13-mediated gene knockdown in promoting xenogeneic cell engraftment.

Conclusions:

  • Cas13-mediated host cell competitiveness reduction is a viable strategy for enhancing interspecies chimera efficiency.
  • This approach offers a new tool for developmental biology and regenerative medicine.
  • Further studies can explore optimizing Cas13 activity and targeting for broader applications in chimera research.

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