CRISPR-HAWK: Haplotype- and Variant-Aware Guide Design Toolkit for CRISPR-Cas.

CRISPR-HAWK reveals that 82.5% of guides across seven therapeutic loci are affected by variants, significantly impacting guide performance in diverse populations.

• Why it matters: Current guide RNA design tools depend on reference genomes and overlook genetic variation, risking reduced efficacy and equity in genome editing therapies across populations.
• What they did: The framework integrates individual- and population-scale variants and haplotypes into guide design, analyzing 79,648 genomes and identifying variants that alter on-target activity and create novel guides.
• The result: Variant-aware guide selection is shown to be essential for equitable genome editing, with some haplotypes completely abolishing predicted activity and variants generating individual-specific guides.