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A toolbox for conditional control of gene expression in apicomplexan parasites
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-09-26 , DOI: 10.1111/mmi.14821
Sylvie Briquet 1 , Mathieu Gissot 2 , Olivier Silvie 1
Affiliation  

Apicomplexan parasites encompass diverse pathogens for humans and animals, including the causative agents of malaria and toxoplasmosis, Plasmodium spp. and Toxoplasma gondii. Genetic manipulation of these parasites has become central to explore parasite biology, unravel gene function and identify new targets for therapeutic strategies. Tremendous progress has been achieved over the past years with the advent of next generation sequencing and powerful genome editing methods. In particular, various methods for conditional gene expression have been developed in both Plasmodium and Toxoplasma to knockout or knockdown essential genes, or for inducible expression of master developmental regulators or mutant versions of proteins. Conditional gene expression can be achieved at three distinct levels. At the DNA level, inducible site-specific recombinases allow conditional genome editing. At the RNA level, regulation can be achieved during transcription, using stage-specific or regulatable promoters, or post-transcriptionally through alteration of mRNA stability or translation. At the protein level, several systems have been developed for inducible degradation or displacement of a protein of interest. In this review, we provide an overview of current systems for conditional control of gene expression in Plasmodium and Toxoplasma parasites, highlighting the advantages and limitations of each approach.

中文翻译:

顶复门寄生虫基因表达条件控制工具箱

顶复门寄生虫包括人类和动物的多种病原体,包括疟疾和弓形虫病的病原体,疟原虫属。和弓形虫。这些寄生虫的基因操作已成为探索寄生虫生物学、揭示基因功能和确定治疗策略新靶点的核心。随着下一代测序和强大的基因组编辑方法的出现,在过去几年中取得了巨大的进步。特别是,已经在疟原虫弓形虫中开发了各种条件基因表达方法敲除或敲除必需基因,或用于主要发育调节因子或蛋白质突变体的可诱导表达。条件基因表达可以在三个不同的水平上实现。在 DNA 水平上,可诱导的位点特异性重组酶允许有条件的基因组编辑。在 RNA 水平上,可以在转录过程中使用特定阶段或可调节的启动子来实现调节,或者在转录后通过改变 mRNA 稳定性或翻译来实现调节。在蛋白质水平上,已经开发了几种用于感兴趣蛋白质的可诱导降解或置换的系统。在这篇综述中,我们概述了当前用于条件控制疟原虫弓形虫基因表达的系统寄生虫,强调每种方法的优点和局限性。
更新日期:2021-09-26
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