Guide Swap enables genome-scale pooled CRISPR-Cas9 screening in human primary cells.CRISPR-Cas9 screening allows genome-wide interrogation of gene function.  Guide Swap permits genome-scale pooled CRISPR-Cas9 screening in human primary cells by exploiting the unexpected finding that editing by lentivirally delivered, targeted guide RNAs (gRNAs) occurs efficiently when Cas9 is introduced in complex with nontargeting gRNA.  We validated Guide Swap in depletion and enrichment screens in CD4+ T cells.  Next, we implemented Guide Swap in a model of ex vivo hematopoiesis, and identified known and previously unknown regulators of CD34+ hematopoietic stem and progenitor cell (HSPC) expansion. 
Guide Swap
Guide Swap enables genome-scale pooled CRISPR-Cas9 screening in human primary cells.CRISPR-Cas9 screening allows genome-wide interrogation of gene function.  Guide Swap permits genome-scale pooled CRISPR-Cas9 screening in human primary cells by exploiting the unexpected finding that editing by lentivirally delivered, targeted guide RNAs (gRNAs) occurs efficiently when Cas9 is introduced in complex with nontargeting gRNA. 
CRISPR-Cas9 screening
Guide Swap permits genome-scale pooled CRISPR-Cas9 screening in human primary cells by exploiting the unexpected finding that editing by lentivirally delivered, targeted guide RNAs (gRNAs) occurs efficiently when Cas9 is introduced in complex with nontargeting gRNA. 
lentivirally delivered
Guide Swap permits genome-scale pooled CRISPR-Cas9 screening in human primary cells by exploiting the unexpected finding that editing by lentivirally delivered, targeted guide RNAs (gRNAs) occurs efficiently when Cas9 is introduced in complex with nontargeting gRNA. 
guide RNAs (gRNAs)
Guide Swap enables genome-scale pooled CRISPR-Cas9 screening in human primary cells.CRISPR-Cas9 screening allows genome-wide interrogation of gene function.  Currently, to achieve the high and uniform Cas9 expression desirable for screening, one needs to engineer stable and clonal Cas9-expressing cells-an approach that is not applicable in human primary cells.  Guide Swap permits genome-scale pooled CRISPR-Cas9 screening in human primary cells by exploiting the unexpected finding that editing by lentivirally delivered, targeted guide RNAs (gRNAs) occurs efficiently when Cas9 is introduced in complex with nontargeting gRNA. 
Cas9