Related Experiment Video

Updated: Jul 24, 2025

A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells
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A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells

Published on: August 25, 2017

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CRISPR prime editing for unconstrained correction of oncogenic KRAS variants

Gayoung Jang1,2, Jiyeon Kweon1, Yongsub Kim3,4

  • 1Department of Cell and Genetic Engineering, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Communications Biology
|June 30, 2023
PubMed

Insights

Scientists developed universal prime editing guide RNAs (pegRNAs) to correct common KRAS oncogene mutations. This approach shows promise as a versatile therapeutic strategy for various KRAS-driven cancers.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • KRAS mutations are prevalent in many cancers, driving tumor growth.
  • Diverse KRAS mutations present challenges for developing targeted therapies.
  • The RAS family includes KRAS as the most frequently mutated gene.

Purpose of the Study:

  • To develop a universal prime editing guide RNA (pegRNA) for KRAS mutations.
  • To assess the efficacy of prime editing in correcting oncogenic KRAS variants.
  • To explore a potential 'one-to-many' therapeutic strategy for KRAS-driven cancers.

Main Methods:

  • Development of universal pegRNAs targeting G12 and G13 KRAS mutations.
  • CRISPR-mediated prime editing (PE) system utilization.
  • Testing in HEK293T/17 cells and human cancer cell lines with endogenous mutations.

Main Results:

  • Universal pegRNA corrected 12 KRAS mutation types (94% of known variants) with up to 54.8% efficiency in cell lines.
  • Successful correction of endogenous G13D KRAS mutation in human cancer cells.
  • Achieved up to 40.6% correction frequency for G13D mutation without inducing indel mutations.

Conclusions:

  • Prime editing with universal pegRNAs offers a promising strategy for targeting multiple KRAS oncogene variants.
  • This approach could provide a versatile therapeutic option for a broad spectrum of KRAS-mutated cancers.
  • The developed universal pegRNA demonstrates significant potential for clinical application in precision oncology.

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