CRISPRi: a way to integrate iPSC-derived neuronal models

Journal article : Review

The genetic landscape of neurodegenerative diseases encompasses genes affecting multiple cellular pathways which exert effects in an array of neuronal and glial cell-types. Deconvolution of the roles of genes implicated in disease and the effects of disease-associated variants remains a vital step in the understanding of neurodegeneration and the development of therapeutics. Disease modelling using patient induced pluripotent stem cells (iPSCs) has enabled the generation of key cell-types associated with disease whilst maintaining the genomic variants that predispose to neurodegeneration. The use of CRISPR interference (CRISPRi), alongside other CRISPR-perturbations, allows the modelling of the effects of these disease-associated variants or identifying genes which modify disease phenotypes. This review summarises the current applications of CRISPRi in iPSC-derived neuronal models, such as fluorescence-activated cell sorting (FACS)-based screens, and discusses the future opportunities for disease modelling, identification of disease risk modifiers and target/drug discovery in neurodegeneration.

Authors: Franks, SNJ; Heon-Roberts, R; Ryan, B

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Portland Press
• Journal: Biochemical Society Transactions
• Volume: 52
• Issue: 2
• Pages: 539–551
• Publication date: 2024-03-25
• Acceptance date: 2024-03-13
• DOI: 10.1042/bst20230190
• EISSN: 1470-8752
• ISSN: 0300-5127
• Language: English
• Keywords: Parkinson's disease; functional genomics; neurodegeneration; high-throughput screening; induced pluripotent stem cells; CRISPR
• Subtype: Review