How can CRISPR be used to control gene expression?

• A. Using dead Cas9 fused to activators or repressors (CRISPRa/CRISPRi) to upregulate or downregulate target genes
• B. CRISPR permanently edits the DNA sequence to change gene expression
• C. Only by cutting the DNA to disable genes
• D. CRISPR cannot influence gene expression without altering the DNA sequence

Answer: (A)

Using a non-cutting CRISPR system to control gene expression relies on a catalytically inactive Cas9 (dead Cas9) fused to transcriptional activators or repressors. The guide RNA brings this complex to the gene’s promoter or regulatory region. When it binds, the activator version recruits the transcription machinery to boost transcription, while the repressor version recruits silencing factors to reduce transcription. Since the nuclease is disabled, the DNA sequence isn’t altered, so gene expression is modulated without permanent edits. This is different from approaches that physically cut DNA to disrupt a gene, which cause permanent changes. It also shows that CRISPR can influence expression without changing the sequence at all.