CRISPR knockout screens outperform shRNA and CRISPR-interference screens in a side-by-side comparison.
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High-throughput genetic screens have become essential tools for studying a wide variety of biological processes. Here the scientists experimentally compare systems based on clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) or its transcriptionally repressive variant, CRISPR-interference (CRISPRi), with a traditional short hairpin RNA (shRNA)-based system for performing lethality screens. They find that the CRISPR technology performed best, with low noise, minimal off-target effects and consistent activity across reagents.