CRISPR knockout screening outperforms shRNA and CRISPRi in identifying essential genes

Nat Biotechnol. 2016 Jun;34(6):631-3. doi: 10.1038/nbt.3536. Epub 2016 Apr 25.


High-throughput genetic screens have become essential tools for studying a wide variety of biological processes. Here we 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. We find that the CRISPR technology performed best, with low noise, minimal off-target effects and consistent activity across reagents.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Gene Expression Profiling / methods*
  • Gene Knockout Techniques / methods*
  • Genetic Markers / genetics*
  • Genetic Testing / methods*
  • RNA, Small Interfering / genetics*


  • Genetic Markers
  • RNA, Small Interfering