Optimized CRISPR-Cas12a platform for combinatorial drop-out genetic screening (RNA-seq). Optimized CRISPR-Cas12a platform for combinatorial drop-out genetic screening (RNA-seq)

Combinatorial genetic perturbations have been utilized to identify synthetic sick/lethal genetic interactions for cancer drug target discovery. Current methods for high-throughput combinatorial genetic screening are inefficient and cumbersome. Here we developed a simple, robust, and high-performance CRISPR-Cas12a-based approach for unbiased, combinatorial genetic screening in cancer cells. Overall design: mRNA profiles of Cas12 sgRNA-expressing MLL-AF9 transformed acute myeloid leukemia cells (RN2).