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CRISPRi-Mediated Epigenetic Suppression of TERT Reduces Cell Growth in Non-Small-Cell Lung Cancer Cells

Seong-Ho Park1, Juyoung Hong2, Woochang Hwang3,4

  • 1Department of Life Science, College of Natural Sciences, Hanyang University, Seongdong-gu, Seoul 04763, Republic of Korea.

Cells
|July 13, 2026
PubMed

Insights

CRISPR interference (CRISPRi) using dCas9-KRAB effectively repressed telomerase reverse transcriptase (TERT) expression in lung cancer cells. This novel approach reduced cancer cell viability and growth with minimal off-target effects, offering a promising therapeutic strategy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • Telomerase reverse transcriptase (TERT) is a key driver in most cancers, making it a significant therapeutic target.
  • Existing TERT-targeting methods like chemical inhibitors and siRNA face challenges including limited efficacy and off-target effects.

Purpose of the Study:

  • To evaluate the efficacy of dCas9-KRAB-mediated CRISPR interference (CRISPRi) for transcriptional repression of TERT.
  • To determine if CRISPRi can overcome limitations of conventional TERT-targeting strategies without causing DNA cleavage.

Main Methods:

  • The dCas9-KRAB system was applied to H1299 non-small-cell lung cancer cells.
  • TERT expression levels were quantified.
  • Cell viability and growth were assessed.
  • Transcriptome-wide analysis was performed to detect off-target gene expression changes.

Main Results:

  • TERT expression was reduced by approximately 80% in treated cells.
  • Significant decreases in cancer cell viability and growth were observed.
  • Transcriptome-wide analysis revealed limited detectable changes in non-target gene expression.

Conclusions:

  • dCas9-KRAB-mediated CRISPRi demonstrates proof-of-principle for targeted TERT repression in cancer cells.
  • This method offers a potential strategy for cancer therapy with reduced off-target effects on gene expression.
Keywords:
CRISPR interferenceTERTcancer cellsdCas9-KRABgene regulationtelomerasetranscriptional repression

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