Cornerstones of CRISPR-Cas in drug discovery and therapy

Christof Fellmann; Benjamin G Gowen; Pei-Chun Lin; Jennifer A Doudna; Jacob E Corn

doi:10.1038/nrd.2016.238

Cornerstones of CRISPR-Cas in drug discovery and therapy

Nat Rev Drug Discov. 2017 Feb;16(2):89-100. doi: 10.1038/nrd.2016.238. Epub 2016 Dec 23.

Authors

Christof Fellmann¹, Benjamin G Gowen^{1

2}, Pei-Chun Lin^{1

2

3}, Jennifer A Doudna^{1

4

5

6

7}, Jacob E Corn^{1

2}

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
² Innovative Genomics Institute, University of California, Berkeley, Berkeley, California 94720, USA.
³ Present address: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94158, USA.
⁴ Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA.
⁵ Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California 94720, USA.
⁶ Li Ka Shing Biomedical and Health Sciences Center, University of California, Berkeley, Berkeley, California 94720, USA.
⁷ MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.

Abstract

The recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing and regulation is spurring a revolution in biology. Paired with the rapid expansion of reference and personalized genomic sequence information, technologies based on CRISPR-Cas are enabling nearly unlimited genetic manipulation, even in previously difficult contexts, including human cells. Although much attention has focused on the potential of CRISPR-Cas to cure Mendelian diseases, the technology also holds promise to transform the development of therapies to treat complex heritable and somatic disorders. In this Review, we discuss how CRISPR-Cas can affect the next generation of drugs by accelerating the identification and validation of high-value targets, uncovering high-confidence biomarkers and developing differentiated breakthrough therapies. We focus on the promises, pitfalls and hurdles of this revolutionary gene-editing technology, discuss key aspects of different CRISPR-Cas screening platforms and offer our perspectives on the best practices in genome engineering.

Publication types

Review

MeSH terms

Animals
Biomarkers
CRISPR-Associated Proteins / drug effects*
CRISPR-Cas Systems
Clustered Regularly Interspaced Short Palindromic Repeats / drug effects*
Drug Discovery / trends*
Drug Therapy / trends*
Genetic Engineering
Genetic Therapy / trends
Humans

Substances

Biomarkers
CRISPR-Associated Proteins

Grants and funding

K99 GM118909/GM/NIGMS NIH HHS/United States