In situ CRISPR-Cas9 base editing for the development of genetically engineered mouse models of breast cancer.

ABSTRACT: Genetically engineered mouse models (GEMMs) of cancer have proven to be of great value for basic and translational research. Although CRISPR-based gene disruption offers a fast-track approach for perturbing gene function and circumvents certain limitations of standard GEMM development, it does not provide a flexible platform for recapitulating clinically relevant missense mutations in vivo. To this end, we generated knock-in mice with Cre-conditional expression of a cytidine base editor and tested their utility for precise somatic engineering of missense mutations in key cancer drivers. Upon intraductal delivery of sgRNA-encoding vectors, we could install point mutations with high efficiency in one or multiple endogenous genes in situ and assess the effect of defined allelic variants on ma

SUBMITTER: Annunziato S 

PROVIDER: S-EPMC7049816 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature