Using CRISPR to test the roles of noncoding gene control regions

CRISPR-based screens enable direct perturbation of noncoding cis-regulatory elements (CREs) in their native genomic context.

• The majority of genetic variants linked to traits are found in noncoding regulatory regions, many of which remain uncharacterized.
• Conventional pooled CRISPR screens assign cells based on sgRNA identity rather than the specific genotype introduced.
• Genotype-resolved approaches can directly read the edited endogenous sequence, addressing limitations of traditional methods.
• Sequence variants in CREs are linked to human diseases, suggesting that advancements in CRISPR technology may facilitate new therapeutic developments.
• The review covers various CRISPR-based techniques, their limitations, and emerging methods that could enhance gene therapy and regulatory sequence prediction.

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