Centre de Référence Maladies Rares


Biotherapy of genetic diseases, inflammatory disorders and cancers (BMGIC)

FR: Biologie Fondamentale Appliquée à la Médecine

U1035Display navigation CRISPR-Cas9 molecular scissors: a bit too sharp? FR / EN

New article by the Biotherapy team in Nature Communications published the 08-03-2019

CRISPR-Cas9 genome editing induces megabase-scale chromosomal truncations. Cullot et al. 2019 Nat Commun

CRISPR-Cas9 induces chromosomal extremity loss.

We described that CRISPR-Cas9-nuclease induces high chromosomal toxicity, with megabase-scale chromosomal truncations and duplication exactly starting at CRISPR-Cas9 nuclease DSB. We extend our data from cell lines to primary cells with higher impact for future CRISPR clinical application. We demonstrate that this chromosomal truncation risk is p53-dependent in primary cells. Taken together, this report raises the biosafety issue of CRISPR-Cas9 medical applications, in the same time of several ongoing clinical trials. Even worse, Dr. Jiankui He used CRISPR-Cas9 nuclease to alter the genome of human embryos prior to uterus implantation. It seems to us that the scientific community has to be warned of chromosomal deletion risk. Interestingly, we found that, by contrast to nuclease, single CRISPR-Cas9 nickase approach strongly limit this risk.

The author from the left to the right:
Julian Boutin (AHU-Doc), Aurélie Bedel (MCU-PH), Grégoire Cullot (Doc), François Moreau-Gaudry (PU-PH)

Julian Boutin, Aurélie Bedel, Grégoire Cullot, François Moreau-Gaudry
Article reference : DOI 10.1038/s41467-019-09006-2
Contact : gregoire.cullot@u-bordeaux.fr


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