Measuring the Impact of Genetic Heterogeneity and Chromosomal Inversions on the Efficacy of CRISPR-Cas9 Gene Drives in Different Strains of Anopheles gambiae.

IF 3.7 4区 生物学 Q2 GENETICS & HEREDITY CRISPR Journal Pub Date : 2023-10-01 Epub Date: 2023-09-13 DOI:10.1089/crispr.2023.0029
Poppy Pescod, Giulia Bevivino, Amalia Anthousi, Ruth Shelton, Josephine Shepherd, Fabrizio Lombardo, Tony Nolan
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Abstract

The human malaria vector Anopheles gambiae is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site ("homing"), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of laboratory-developed gene drives into wild populations of target species An. gambiae species complex, which show high levels of genome variation. Two gene drives (vas2-5958 and zpg-7280) were introduced into three An. gambiae strains collected across Africa with 5.3-6.6% variation around the target sites, and the effect of this variation on homing was measured. Gene drive homing across different karyotypes of the 2La chromosomal inversion was also assessed. No decrease in gene drive homing was seen despite target site heterology, demonstrating the applicability of gene drives to wild populations.

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测量遗传异质性和染色体反转对CRISPR-Cas9基因驱动在不同冈比亚按蚊菌株中的效力的影响。
人类疟疾媒介冈比亚按蚊对杀虫剂的耐药性越来越强,这推动了基因控制策略的发展。CRISPR-Cas9基因驱动可以通过在高度特异性的靶标上产生双链断裂来修饰群体,触发基因驱动复制到切割位点(“归巢”),确保其遗传。负责的DNA修复机制需要供体和受体染色体之间的同源性,这给实验室开发的基因驱动入侵目标物种野生种群带来了挑战冈比亚物种复合体显示出高水平的基因组变异。将两种基因驱动(vas2-5958和zpg-7280)引入非洲各地采集的三株冈比亚安株中,目标位点周围的变异率为5.3-6.6%,并测量了这种变异对归巢的影响。还评估了2La染色体反转的不同核型之间的基因驱动归巢。尽管靶位点异质性,但基因驱动归巢没有减少,这表明基因驱动对野生种群的适用性。
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来源期刊
CRISPR Journal
CRISPR Journal Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
6.30
自引率
2.70%
发文量
76
期刊介绍: In recognition of this extraordinary scientific and technological era, Mary Ann Liebert, Inc., publishers recently announced the creation of The CRISPR Journal -- an international, multidisciplinary peer-reviewed journal publishing outstanding research on the myriad applications and underlying technology of CRISPR. Debuting in 2018, The CRISPR Journal will be published online and in print with flexible open access options, providing a high-profile venue for groundbreaking research, as well as lively and provocative commentary, analysis, and debate. The CRISPR Journal adds an exciting and dynamic component to the Mary Ann Liebert, Inc. portfolio, which includes GEN (Genetic Engineering & Biotechnology News) and more than 80 leading peer-reviewed journals.
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