Direct capture of CRISPR guides enables scalable, multiplexed, and multi-omic Perturb-seq

Pairing CRISPR-based genetic screens with single-cell transcriptional phenotypes (Perturb-seq) has advanced efforts to explore the function of mammalian genes and genetic networks. We present strategies for Perturb-seq that enable direct capture of CRISPR sgRNAs within 3’ or 5’ single-cell RNA-sequencing libraries using the 10x Genomics platform. This technology greatly expands the accessibility, scalability, and flexibility of Perturb-seq, specifically enabling use with programmed combinatorial perturbations and multiplexing with multi-omic measurements.