Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Sci Adv. 2017 May 19;3(5):e1601910. doi: 10.1126/sciadv.1601910. eCollection 2017 May.
Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle , we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.
基于 CRISPR/Cas9 的合成基因驱动有潜力控制、改变或抑制农作物害虫和疾病媒介种群，但它们在野生种群中的作用尚不清楚。我们利用来自四个粉斑螟种群的遗传数据表明，大多数种群都存在 Cas9 靶标位点的遗传变异，其中一些变异会使它们对驱动（ITD）产生免疫力。我们表明，即使是罕见的 ITD 等位基因也可以降低或消除基于 CRISPR/Cas9 的合成基因驱动的功效。这种影响与轻度近亲繁殖相当，并被放大，而轻度近亲繁殖是许多传播疾病的节肢动物的特征。我们得出结论，设计这种驱动需要对目标种群内部和之间的遗传变异性和交配系统进行特征描述。
