CellsJul 13, 2026

Using gene-silencing to lower TERT activity reduces growth of non-small-cell lung cancer cells

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 14, 2026

Abstract

Reduction in TERT expression was observed up to approximately 80% in H1299 non-small-cell lung cancer cells using dCas9-KRAB-mediated CRISPR interference.

dCas9-KRAB-mediated CRISPR interference effectively repressed TERT without causing DNA cleavage.
Significant decreases in cell viability and growth were noted alongside the reduction in TERT expression.
Transcriptome-wide analysis indicated limited changes in the expression of non-target genes during the experiment.
The findings suggest potential for dCas9-KRAB-mediated CRISPRi as a targeted therapeutic strategy in cancer.

Simplified

TERT, the catalytic subunit of telomerase, is aberrantly activated in most cancers and represents an attractive therapeutic target. However, conventional TERT-targeting strategies, including chemical inhibitors and siRNA, are limited by several issues, such as insufficient efficacy and off-target effects. In this study, we investigated whether dCas9-KRAB-mediated CRISPR interference (CRISPRi) could overcome the limitations by transcriptional repression of TERT without DNA cleavage. We first assessed the efficacy of the dCas9-KRAB system by applying it to H1299 non-small-cell lung cancer cells and observed reduction in TERT expression up to approximately 80% and significant decreases in cell viability and growth. Transcriptome-wide analysis showed limited detectable changes in non-target-gene expression under the conditions tested. Together, the results suggest that dCas9-KRAB-mediated CRISPRi could serve as a proof-of-principle approach for targeted repression of TERT in cancer cells with limited detectable effects on non-target-gene expression.

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Using gene-silencing to lower TERT activity reduces growth of non-small-cell lung cancer cells

Abstract

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