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CRISPR Knockout of NRF2 Reverses Chemotherapy Resistance in Lung Cancer Models

The preclinical study reports restored chemotherapy response in lung squamous cell carcinoma after disabling a tumor-specific NRF2 mutation.

Overview

  • Researchers at ChristianaCare's Gene Editing Institute showed that CRISPR/Cas9 disruption of NRF2 restored drug sensitivity and slowed tumor growth in cell lines and mouse models.
  • The approach targeted the tumor-specific R34G alteration in NRF2, re-sensitizing tumors to standard agents carboplatin and paclitaxel.
  • In mouse studies, CRISPR was delivered with lipid nanoparticles, a non-viral method, and treated tumors responded more effectively to chemotherapy.
  • Sequencing data indicated highly specific on-target editing of NRF2 with minimal off-target changes.
  • Editing roughly 20%–40% of tumor cells was sufficient for therapeutic effect, supporting a path toward clinical testing and potential use in other NRF2-driven cancers.