Disease modeling by efficient genome editing using a near PAM-less base editor in vivo
Marion Rosello,
Malo Serafini,
Luca Mignani,
Dario Finazzi,
Carine Giovannangeli,
Marina C. Mione,
Jean-Paul Concordet () and
Filippo Del Bene ()
Additional contact information
Marion Rosello: Sorbonne Université, INSERM U968, CNRS UMR 7210, Institut de la Vision
Malo Serafini: Sorbonne Université, INSERM U968, CNRS UMR 7210, Institut de la Vision
Luca Mignani: University of Brescia
Dario Finazzi: University of Brescia
Carine Giovannangeli: Muséum National d’Histoire Naturelle, INSERM U1154, CNRS UMR 7196
Marina C. Mione: University of Trento
Jean-Paul Concordet: Muséum National d’Histoire Naturelle, INSERM U1154, CNRS UMR 7196
Filippo Del Bene: Sorbonne Université, INSERM U968, CNRS UMR 7210, Institut de la Vision
Nature Communications, 2022, vol. 13, issue 1, 1-13
Abstract:
Abstract Base Editors are emerging as an innovative technology to introduce point mutations in complex genomes. So far, the requirement of an NGG Protospacer Adjacent Motif (PAM) at a suitable position often limits the base editing possibility to model human pathological mutations in animals. Here we show that, using the CBE4max-SpRY variant recognizing nearly all PAM sequences, we could introduce point mutations for the first time in an animal model with high efficiency, thus drastically increasing the base editing possibilities. With this near PAM-less base editor we could simultaneously mutate several genes and we developed a co-selection method to identify the most edited embryos based on a simple visual screening. Finally, we apply our method to create a zebrafish model for melanoma predisposition based on the simultaneous base editing of multiple genes. Altogether, our results considerably expand the Base Editor application to introduce human disease-causing mutations in zebrafish.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31172-z
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DOI: 10.1038/s41467-022-31172-z
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