20 Jan Nature Communications publication – team 8 – genotoxic effects of CRISPR-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
Congratulation to BRIC Team 8 for their last publication in Nature Communications!!!
Their study, in collaboration with EFS Nouvelle Aquitaine and Gustave-Roussy Institute genomic platform , introduces a powerful single-cell multiplex platform to sensitively map on-target genotoxic effects of CRISPR-Cas9 genome editing in primary human cells. By combining single-cell DNA sequencing (scSNP-DNA-seq) with cytometric assays for micronuclei and loss of heterozygosity, the Team detected and characterized chromosomal instability at edited loci with unprecedented resolution Importantly, they show that the drug palbociclib can prevent chromosomal rearrangements in hematopoietic stem cells without compromising cell fate or engraftment (patent). Unexpectedly, inhibition of DNA-PKcs increases short-term risks but disappear after long-term graft. This work provides a critical tool and strategy for improving the safety assessment of CRISPR-based therapies.
This work was supported by the French national research agency (ANR) , by Agence de Biomédecine , by la Fondation pour la Recherche Médicale and AFM telethon . We thank INSERM transfert for valorization assistance.
Boutin J*, Fayet S*, Marin V*, Bergès C*, Riandière M, Toutain J, Lamrissi-Garcia I, Thibault C, Cappellen D, Dabernat S, Poulet A, Francillette M, Droin N, Debeissat C, Brunet de la Grange P, Moreau-Gaudry F*, Bedel A*. “Single-cell multiplex approaches deeply map ON-target CRISPR-genotoxicity and reveal its mitigation by palbociclib and long-term engraftment”. Nat Commun. 2026 Jan 10. doi: 10.1038/s41467-025-68177-3. PMID: 41519897.
Patent: PCT/EP2024/062916 for palbociclib to prevent CRISPR genotoxicity
From left to right: François Moreau-Gaudry, Victor Marin, Aurélie Bedel, Sabrinat Fayet, Julian Boutin, Camille Bergès
