Fiche publication
Date publication
septembre 2025
Journal
Nature biotechnology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CULLOT Grégoire
Tous les auteurs :
Gupta D, Patinios C, Bassett HV, Kibe A, Collins SP, Kamm C, Wang Y, Zhao C, Vollen K, Toussaint C, Calvin I, Cullot G, Aird EJ, Polkoff KM, Nguyen-Vo TP, Migur A, Schut F, Al'Abri IS, Achmedov T, Del Re A, Corn JE, Saliba AE, Crook N, Stepanova AN, Alonso JM, Beisel CL
Lien Pubmed
Résumé
Base editors create precise genomic edits by directing nucleobase deamination or removal without inducing double-stranded DNA breaks. However, a vast chemical space of other DNA modifications remains to be explored for genome editing. Here we harness the bacterial antiphage toxin DarT2 to append ADP-ribosyl moieties to DNA, unlocking distinct editing outcomes in bacteria versus eukaryotes. Fusing an attenuated DarT2 to a Cas9 nickase, we program site-specific ADP-ribosylation of thymines within a target DNA sequence. In tested bacteria, targeting drives homologous recombination, offering flexible and scar-free genome editing without base replacement or counterselection. In tested yeast, plant and human cells, targeting drives substitution of the modified thymine to adenine or a mixture of adenine and cytosine with limited insertions or deletions, offering edits inaccessible to current base editors. Altogether, our approach, called append editing, leverages the addition of chemical moieties to DNA to expand current modalities for precision gene editing.
Référence
Nat Biotechnol. 2025 09 4;:
