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Related Concept Videos

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CRISPR/Cas9 Genome Editing

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The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
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Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
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Related Experiment Video

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Efficient and multiplexed somatic genome editing with Cas12a mice.

Jess D Hebert1, Haiqing Xu2, Yuning J Tang1

  • 1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.

Nature Biomedical Engineering
|May 30, 2025
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Summary

Researchers developed new mouse models using enhanced Acidaminococcus sp. Cas12a (enAsCas12a) for precise somatic genome editing. These models efficiently create complex genetic alterations, advancing the study of gene interactions in vivo.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Somatic genome editing in mice advances in vivo genetic alteration studies.
  • Current models have limited capacity for multiple targeted edits, restricting the study of complex genetic interactions.

Purpose of the Study:

  • To develop a novel transgenic mouse model for efficient generation of compound genotypes using enhanced Acidaminococcus sp. Cas12a (enAsCas12a).
  • To enable high-throughput in vivo investigation of complex genetic interactions and their role in disease, particularly cancer.

Main Methods:

  • Generation of transgenic mice with Cre-regulated and constitutive enAsCas12a expression.
  • Integration of modular CRISPR RNA (crRNA) arrays with clonal barcoding to quantify tumor formation and growth.
  • Systematic inactivation of combinations of nine tumor suppressor genes.

Main Results:

  • The enAsCas12a system robustly generated compound genotypes, including cancers from tumor suppressor gene inactivation and oncogenic translocations.
  • Clonal barcoding quantified tumor characteristics and the impact of guide RNA number and position.
  • Inactivation of nine tumor suppressor genes revealed that triple-knockout genotype fitness is predictable from single- and double-gene effects.

Conclusions:

  • The developed enAsCas12a mouse models facilitate rapid creation of complex genetic disease models.
  • This system enables high-throughput in vivo investigation of coincident genomic alterations.
  • Findings suggest that complex genetic interactions in cancer may be largely driven by additive effects of individual gene alterations.