title: Cornerstones of CRISPR-Cas in drug discovery and therapy.
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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Christof
authors.initials: C
authors.lastname: Fellmann
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.|Innovative Genomics Institute, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Gowen
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.|Innovative Genomics Institute, University of California, Berkeley, Berkeley, California 94720, USA.|Present address: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Lin
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.|Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA.|Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California 94720, USA.|Li Ka Shing Biomedical and Health Sciences Center, University of California, Berkeley, Berkeley, California 94720, USA.|MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doudna
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.|Innovative Genomics Institute, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Corn
mesh_terms: D000818:Animals; D015415:Biomarkers; D064130:CRISPR-Associated Proteins / Q000187:drug effects*; D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000187:drug effects*; D055808:Drug Discovery / Q000639:trends*; D004358:Drug Therapy / Q000639:trends*; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000639:trends; D006801:Humans
chemical_list: D015415:Biomarkers; D064130:CRISPR-Associated Proteins