Base editing sensor libraries for high-throughput engineering and functional analysis of cancer-associated single nucleotide variants.

ABSTRACT: Base editing can be applied to characterize single nucleotide variants of unknown function, yet defining effective combinations of single guide RNAs (sgRNAs) and base editors remains challenging. Here, we describe modular base-editing-activity 'sensors' that link sgRNAs and cognate target sites in cis and use them to systematically measure the editing efficiency and precision of thousands of sgRNAs paired with functionally distinct base editors. By quantifying sensor editing across >200,000 editor-sgRNA combinations, we provide a comprehensive resource of sgRNAs for introducing and interrogating cancer-associated single nucleotide variants in multiple model systems. We demonstrate that sensor-validated tools streamline production of in vivo cancer models and that integrating sensor modules

SUBMITTER: Sanchez-Rivera FJ 

PROVIDER: S-EPMC9232935 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature