Applications of CRISPR genome editing technology in drug target identification and validation

Expert Opin Drug Discov. 2017 Jun;12(6):541-552. doi: 10.1080/17460441.2017.1317244. Epub 2017 Apr 23.


The analysis of pharmaceutical industry data indicates that the major reason for drug candidates failing in late stage clinical development is lack of efficacy, with a high proportion of these due to erroneous hypotheses about target to disease linkage. More than ever, there is a requirement to better understand potential new drug targets and their role in disease biology in order to reduce attrition in drug development. Genome editing technology enables precise modification of individual protein coding genes, as well as noncoding regulatory sequences, enabling the elucidation of functional effects in human disease relevant cellular systems. Areas covered: This article outlines applications of CRISPR genome editing technology in target identification and target validation studies. Expert opinion: Applications of CRISPR technology in target validation studies are in evidence and gaining momentum. Whilst technical challenges remain, we are on the cusp of CRISPR being applied in complex cell systems such as iPS derived differentiated cells and stem cell derived organoids. In the meantime, our experience to date suggests that precise genome editing of putative targets in primary cell systems is possible, offering more human disease relevant systems than conventional cell lines.

Keywords: CRISPR; drug discovery; genome editing; target validation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Line
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Drug Design*
  • Drug Discovery / methods
  • Drug Industry / methods
  • Gene Editing / methods*
  • Genome, Human
  • Humans
  • Molecular Targeted Therapy
  • Treatment Failure
  • Validation Studies as Topic