Disease Modeling by Efficient Genome Editing Using a Near PAM-less Base Editor in Vivo

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jun 14

PMID 35701478

Authors

Marion Rosello

Malo Serafini

Luca Mignani

Dario Finazzi

Carine Giovannangeli

Marina C Mione

Jean-Paul Concordet

Filippo Del Bene

Affiliations

Soon will be listed here.

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.

Citing Articles

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