Unraveling CRISPR-Cas9 genome engineering parameters via a library-on-library approach.

Chari, Raj; Mali, Prashant; Moosburner, Mark; Church, George M · Nat Methods · 2015

basic_science · Level V

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Abstract

We developed an in vivo library-on-library methodology to simultaneously assess single guide RNA (sgRNA) activity across ∼1,400 genomic loci. Assaying across multiple human cell types and end-processing enzymes as well as two Cas9 orthologs, we unraveled underlying nucleotide sequence and epigenetic parameters. Our results and software (http://crispr.med.harvard.edu/sgRNAScorer) enable improved design of reagents, shed light on mechanisms of genome targeting, and provide a generalizable framework to study nucleic acid-nucleic acid interactions and biochemistry in high throughput.

Medical subject headings