Evaluation of RNAi and CRISPR technologies by large-scale gene expression profiling in the Connectivity Map.

ABSTRACT: The application of RNA interference (RNAi) to mammalian cells has provided the means to perform phenotypic screens to determine the functions of genes. Although RNAi has revolutionized loss-of-function genetic experiments, it has been difficult to systematically assess the prevalence and consequences of off-target effects. The Connectivity Map (CMAP) represents an unprecedented resource to study the gene expression consequences of expressing short hairpin RNAs (shRNAs). Analysis of signatures for over 13,000 shRNAs applied in 9 cell lines revealed that microRNA (miRNA)-like off-target effects of RNAi are far stronger and more pervasive than generally appreciated. We show that mitigating off-target effects is feasible in these datasets via computational methodologies to produce a consensus

SUBMITTER: Smith I 

PROVIDER: S-EPMC5726721 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature