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. Author manuscript; available in PMC: 2024 Jan 11.
Published in final edited form as: Nat Rev Rheumatol. 2021 Jun 29;17(8):462–474. doi: 10.1038/s41584-021-00637-8

Fig. 2 ∣. Genomic editing to investigate regions of interest in rheumatic diseases.

Fig. 2 ∣

A region of interest (for example, a gene or a regulatory non-coding region of interest) can be investigated using a number of genomic editing techniques. a ∣ CRISPR–Cas mutagenesis involves the generation of an array of small insertions or deletions (indels) in the region of interest following cleavage by the Cas nuclease. b ∣ Cas nuclease-mediated deletion can also be used to delete large sections of the region of interest. c ∣ CRISPR–Cas activation (CRISPRa) involves the fusion of proteins that activate gene expression, such as transcriptional activators, enzymes involved in DNA demethylation or histone modifiers that promote DNA accessibility, to a nuclease-deactivated Cas9 protein (dCas9) for targeted promotion of gene expression. d ∣ CRISPR–Cas interference (CRISPRi) involves the fusion of proteins that repress gene expression, such as transcriptional repressors, enzymes involved in DNA methylation (Me) or histone modifiers that epigenetically silence the area, to dCas9 for targeted repression of gene expression.