CRISPR guide-RNA libraries have been iteratively optimised to provide increasingly efficient reagents although their large size is a barrier for some applications. We designed a minimal genome-wide human CRISPR-Cas9 library (MinLibCas9), optimised by mining existing large-scale gene loss-of-function datasets, resulting in a greater than 46% reduction in size compared to other libraries while preserving assay sensitivity and specificity. MinLibCas9 improves the efficiency of CRISPR-Cas9 loss-of-function screens and expands their application to complex models and assays.

Minimal genome-wide human CRISPR-Cas9 library