Selective targeting of KRAS oncogenic alleles by CRISPR/Cas9 inhibits proliferation of cancer cells

Wookjae Lee, Joon Ho Lee, Soyeong Jun, Ji Hyun Lee, Duhee Bang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mutations within the KRAS oncogene are associated with the proliferation of various cancers. Therapeutic approaches for treating cancers with such mutations have focused on targeting the downstream protein effectors of KRAS. However, to date, no approved treatment has targeted the mutated KRAS oncogene directly. Presently, we used the selectivity of the CRISPR/Cas9 system to directly target mutated KRAS alleles. We designed single-guide RNAs (sgRNAs) to target two specific single-nucleotide missense mutations on KRAS codon-12 located in the seed region adjacent to a protospacer adjacent motif (PAM). Lentiviral transduction of Cas9 and the sgRNAs into cancer cells with respective KRAS mutations resulted in high frequency of indels in the seed region. Indel-associated disruption of the mutant KRAS alleles correlated with reduced viability of the cancer cells. The results indicate that CRISPR-Cas9-mediated genome editing can potentially be used for the treatment of cancer patients, specifically those with oncogenic KRAS mutations.

Original languageEnglish
Article number11879
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Clustered Regularly Interspaced Short Palindromic Repeats
Alleles
Cell Proliferation
Guide RNA
Mutation
Neoplasms
Oncogenes
Seeds
Protein Transport
Missense Mutation
Codon
Cell Survival
Therapeutics
Nucleotides

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lee, Wookjae ; Lee, Joon Ho ; Jun, Soyeong ; Lee, Ji Hyun ; Bang, Duhee. / Selective targeting of KRAS oncogenic alleles by CRISPR/Cas9 inhibits proliferation of cancer cells. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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abstract = "Mutations within the KRAS oncogene are associated with the proliferation of various cancers. Therapeutic approaches for treating cancers with such mutations have focused on targeting the downstream protein effectors of KRAS. However, to date, no approved treatment has targeted the mutated KRAS oncogene directly. Presently, we used the selectivity of the CRISPR/Cas9 system to directly target mutated KRAS alleles. We designed single-guide RNAs (sgRNAs) to target two specific single-nucleotide missense mutations on KRAS codon-12 located in the seed region adjacent to a protospacer adjacent motif (PAM). Lentiviral transduction of Cas9 and the sgRNAs into cancer cells with respective KRAS mutations resulted in high frequency of indels in the seed region. Indel-associated disruption of the mutant KRAS alleles correlated with reduced viability of the cancer cells. The results indicate that CRISPR-Cas9-mediated genome editing can potentially be used for the treatment of cancer patients, specifically those with oncogenic KRAS mutations.",
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Selective targeting of KRAS oncogenic alleles by CRISPR/Cas9 inhibits proliferation of cancer cells. / Lee, Wookjae; Lee, Joon Ho; Jun, Soyeong; Lee, Ji Hyun; Bang, Duhee.

In: Scientific reports, Vol. 8, No. 1, 11879, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Bang, Duhee

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