CRISPR-HAWK 发布：整合单倍型与变异的 CRISPR-Cas 向导设计工具
CRISPR-HAWK: haplotype- and variant-aware guide design toolkit for CRISPR-Cas
CRISPR-HAWK 是一个把个体和群体尺度的变异与单倍型纳入 gRNA 设计的框架，代码已在 GitHub 开源。作者在 79 648 个基因组上分析治疗靶点，发现变异会显著改变向导表现：针对 BCL11A 的镰状细胞病治疗向导存在完全消除预测切割活性的单倍型，七个治疗位点中 82.5% 的向导带有影响在靶活性的变异，变异还会产生新的 PAM 位点、带来参考基因组设计看不到的个体特异性向导。
来源：Bioinformatics · academic.oup.com
该工具把个体与群体层面的变异和单倍型纳入 gRNA 设计，并给出 79 648 个基因组上的评估结果，可供做 CRISPR 靶点选择时参考。
摘要
动机
Current CRISPR guide RNA design tools rely on reference genomes, overlooking how genetic variation impacts editing outcomes. As genome editing advances toward clinical applications, incorporating population diversity becomes essential for ensuring therapeutic efficacy across diverse populations.
结果
We present CRISPR-HAWK, a framework integrating individual- and population-scale variants and haplotypes into gRNA design. Analyzing therapeutic targets across 79 648 genomes reveals that genetic variants substantially alter guide performance. For the clinically approved sickle cell disease therapeutic guide targeting BCL11A, we identify haplotypes that completely abolish predicted cutting activity. Across seven therapeutic loci, 82.5% of guides contain variants modifying on-target activity. Variants also create novel protospacer adjacent motif sites generating individual-specific guides invisible to reference-based design. These findings demonstrate that variant-aware selection is critical for equitable genome editing.
可用性
CRISPR-HAWK is available at https://github.com/pinellolab/CRISPR-HAWK and https://github.com/InfOmics/CRISPR-HAWK.