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哺乳动物寄生线虫功能基因组学的最新进展。

Recent advances in functional genomics for parasitic nematodes of mammals.

机构信息

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92161, USA.

出版信息

J Exp Biol. 2020 Feb 7;223(Pt Suppl 1):jeb206482. doi: 10.1242/jeb.206482.

Abstract

Human-parasitic nematodes infect over a quarter of the world's population and are a major cause of morbidity in low-resource settings. Currently available treatments have not been sufficient to eliminate infections in endemic areas, and drug resistance is an increasing concern, making new treatment options a priority. The development of new treatments requires an improved understanding of the basic biology of these nematodes. Specifically, a better understanding of parasitic nematode development, reproduction and behavior may yield novel drug targets or new opportunities for intervention such as repellents or traps. Until recently, our ability to study parasitic nematode biology was limited because few tools were available for their genetic manipulation. This is now changing as a result of recent advances in the large-scale sequencing of nematode genomes and the development of new techniques for their genetic manipulation. Notably, skin-penetrating gastrointestinal nematodes in the genus are now amenable to transgenesis, RNAi and CRISPR/Cas9-mediated targeted mutagenesis, positioning the species as model parasitic nematode systems. A number of other mammalian-parasitic nematodes, including the giant roundworm and the tissue-dwelling filarial nematode , are also now amenable to transgenesis and/or RNAi in some contexts. Using these tools, recent studies of species have already provided insight into the molecular pathways that control the developmental decision to form infective larvae and that drive the host-seeking behaviors of infective larvae. Ultimately, a mechanistic understanding of these processes could lead to the development of new avenues for nematode control.

摘要

人体寄生线虫感染了全球超过四分之一的人口,是资源匮乏地区发病率的主要原因。目前可用的治疗方法不足以消除流行地区的感染,而且耐药性日益令人担忧,因此新的治疗方法成为当务之急。开发新的治疗方法需要更好地了解这些线虫的基本生物学。具体来说,更好地了解寄生线虫的发育、繁殖和行为可能会产生新的药物靶点或新的干预机会,如驱虫剂或诱捕器。直到最近,我们研究寄生线虫生物学的能力还受到限制,因为很少有工具可用于对其进行遗传操作。这一情况正在发生改变,原因是线虫基因组大规模测序的最新进展以及遗传操作新技术的发展。值得注意的是,现在可以对 属的穿透皮肤的胃肠道线虫进行转基因、RNAi 和 CRISPR/Cas9 介导的靶向诱变,使 物种成为有前途的寄生线虫模型系统。其他一些哺乳动物寄生线虫,包括巨大的圆线虫和组织内寄生的丝虫,在某些情况下也可以进行转基因和/或 RNAi。利用这些工具,对 物种的最近研究已经深入了解了控制形成感染性幼虫的发育决策的分子途径,并驱动了感染性幼虫的宿主寻找行为。最终,对这些过程的机制理解可能会开辟线虫控制的新途径。

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