A kinetic model predicts SpCas9 activity, improves off-target classification, and reveals the physical basis of targeting fidelity

Abstract

Cas9 off-target sites can be predicted by many bioinformatics tools. Here the authors present low complexity mechanistic model that characterizes SpCas9 kinetics in free-energy terms, allowing quantitative prediction of off-target activity in bulk-biochemistry, single molecule, and whole-genome profiling experiments.