ArticleLaboratory investigation; a journal of technical methods and pathology2018
Specific targeting of point mutations in EGFR L858R-positive lung cancer by CRISPR/Cas9.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- CRISPR Technology: Transforming the Future of Medicine and Diagnostics.Biochemistry · 2025Review
- CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential.Cell proliferation · 2025Article
- The CRISPR-Cas revolution in head and neck cancer: a new era of targeted therapy.Functional & integrative genomics · 2025Review
- Advancements in Gene Therapy for Non-Small Cell Lung Cancer: Current Approaches and Future Prospects.Genes · 2025Review
- Exosomes for CRISPR-Cas9 Delivery: The Cutting Edge in Genome Editing.Molecular biotechnology · 2024Review
- Targeting DLBCL by mutation-specific disruption of cancer-driving oncogenes.Frontiers in genome editing · 2024Article
- Application and perspective of CRISPR/Cas9 genome editing technology in human diseases modeling and gene therapy.Frontiers in genetics · 2024Review
- CRISPR-Cas9 in basic and translational aspects of cancer therapy.BioImpacts : BI · 2024Review
- Nrf2, A Target for Precision Oncology in Cancer Prognosis and Treatment.Journal of cancer prevention · 2023Review
- Review
- Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy.Cellular and molecular life sciences : CMLS · 2023Review
- Review
- Applications and advancements of CRISPR-Cas in the treatment of lung cancer.Frontiers in cell and developmental biology · 2023Review
- Applications of CRISPR/Cas technology against drug-resistant lung cancers: an update.Molecular biology reports · 2022Review
- Current updates of CRISPR/Cas9-mediated genome editing and targeting within tumor cells: an innovative strategy of cancer management.Cancer communications (London, England) · 2022Review
- Review
- CRISPER/CAS System, a Novel Tool of Targeted Therapy of Drug-Resistant Lung Cancer.Advanced pharmaceutical bulletin · 2022Review
- Targeting Cancer with CRISPR/Cas9-Based Therapy.International journal of molecular sciences · 2022Review
- CRISPR-Cas deployment in non-small cell lung cancer for target screening, validations, and discoveries.Cancer gene therapy · 2021Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells are defined genetically by the mutations they harbor, commonly single nucleotide substitutions. Therapeutic approaches which specifically target cancer cells by recognizing these defining genetic aberrations are expected to exhibit minimal side-effects. However, current protein-based targeted therapy is greatly limited by the range of genes that can be targeted, as well as by acquired resistance. We hypothesized that a therapeutic oligonucleotide-based strategy may address this need of specific cancer targeting. We used CRISPR/Cas9 system to target a commonly occurring EGFR point mutation, L858R, with an oligonucleotide guide that recognizes L858R as the suitable protospacer-adjacent motif (PAM) sequence for DNA cleavage. We found that this strategy, which utilized PAM to differentiate cancer mutation from normal, afforded high specificity to the extent of a single nucleotide substitution. The anti-L858R vehicle resulted in selective genome cleavage only in L858R mutant cells, as detected by Sanger sequencing and T7 Endonuclease I assay. Wild-type cells were unaffected by the same treatment. Digital PCR revealed 37.9 ± 8.57% of L858R gene copies were targeted in mutant. Only treated mutant cells, but not wild-type cells, showed reduction in EGFR expression and decreased cell proliferation. Treated mutant cells also formed smaller tumor load in vivo. This targeting approach is expected to be able to target a significant subset of the 15-35% cancer mutations with C > G, A > G, and T > G point mutations. Thus, this strategy may serve as a useful approach to target cancer-defining mutations with specificity, to the extent of differentiating the change of a single nucleotide.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.