CRISPR activation screens: navigating technologies and applications

• Published in: Trends in biotechnology (Regular ed.) 2024-08, Vol.42 (8), p.1017-1034
• Main Authors: Clark, Teleri, Waller, Matthew A., Loo, Lipin, Moreno, Cesar L., Denes, Christopher E., Neely, G. Gregory
• Format: Article
• Language: English
• Subjects: Animals; Clustered Regularly Interspaced Short Palindromic Repeats - genetics; CRISPR; CRISPR screens; CRISPR-Cas Systems - genetics; CRISPRa; gene activation; Gene Editing - methods; Gene expression; Genetic screening; Genetic Testing - methods; Humans; MicroRNAs; Molecular biology; Peptides; Phenotypes; Proteins; Stem cells; Transcription activation; Transcription factors
• ISSN: 0167-7799; 1879-3096; 1879-3096
• DOI: 10.1016/j.tibtech.2024.02.007

Clustered regularly interspaced short palindromic repeats (CRISPR) activation (CRISPRa) technology allows pooled or targeted upregulation of gene expression. This new technical capacity helps to identify genes that, when upregulated, modify cell physiology and/or disease progression.Various CRISPR activation strategies have been described, with single and combinatorial activator domains enhancing gene activation efficiency. Different activation domains are suited to specific genes and cell types.CRISPRa pooled screening has enabled diverse applications in drug discovery, providing new insight into cell responses and cell differentiation, and even an understanding of SARS-CoV-2 mechanisms during infection.CRISPRa also demonstrates strong potential for in vivo applications for various diseases and conditions. Clustered regularly interspaced short palindromic repeats (CRISPR) activation (CRISPRa) has become an integral part of the molecular biology toolkit. CRISPRa genetic screens are an exciting high-throughput means of identifying genes the upregulation of which is sufficient to elicit a given phenotype. Activation machinery is continually under development to achieve greater, more robust, and more consistent activation. In this review, we offer a succinct technological overview of available CRISPRa architectures and a comprehensive summary of pooled CRISPRa screens. Furthermore, we discuss contemporary applications of CRISPRa across broad fields of research, with the aim of presenting a view of exciting emerging applications for CRISPRa screening. Clustered regularly interspaced short palindromic repeats (CRISPR) activation (CRISPRa) has become an integral part of the molecular biology toolkit. CRISPRa genetic screens are an exciting high-throughput means of identifying genes the upregulation of which is sufficient to elicit a given phenotype. Activation machinery to achieve greater, more robust, and more consistent activation is continually under development. In this review, we offer a succinct technological overview of available CRISPRa architectures and a comprehensive summary of pooled CRISPRa screens. Furthermore, we discuss contemporary applications of CRISPRa across broad fields of research, with the aim of presenting a view of exciting emerging applications for CRISPRa screening.