4.7 Article

i-CRISPR: a personalized cancer therapy strategy through cutting cancer-specific mutations

Journal

MOLECULAR CANCER
Volume 21, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12943-022-01612-x

Keywords

Cancer mutation sequencing; CRISPR-Cas9; Gene editing; DNA damage repair

Funding

  1. China National Key Research and Development Program Stem Cell
  2. Translational Research Key Projects [2018YFA0108300]
  3. National Natural Science Foundation of China [81972968, 82173462, 11635014, 81803168, 81972397, 31971109]
  4. Shanghai Rising Star Program [22QA1411500]
  5. Three Year Plan of Shanghai Municipal Health Commission [GWV-10.2-YQ27, 20214Y0012]
  6. National Military Grants [AEP17J001]
  7. Naval Medical University [WS-WL-02]
  8. Shanghai Key Laboratory of Cell Engineering [14DZ2272300]

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This study developed a new precise personalized strategy, named i-CRISPR, for cancer treatment by adding DNA damage repair inhibitors (i) and inducing cancer cell-specific DNA double strand breaks using CRISPR. The efficacy of this strategy was confirmed in multiple cancer models through in vitro and in vivo experiments, and the mechanism of cell death was revealed.
Developing a strategy to specifically kill cancer cells without inducing obvious damage to normal cells may be of great clinical significance for cancer treatment. In the present study, we developed a new precise personalized strategy named i-CRISPR for cancer treatment through adding DNA damage repair inhibitors(i) and inducing cancer cell-specific DNA double strand breaks by CRISPR. Through in vitro and in vivo experiments, we confirmed the efficacy of this strategy in multiple cancer models and revealed the mechanism of cell death. Our strategy might provide a novel concept for precise cancer therapy.

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