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报告基因与转基因(动质体目,锥虫科):用于筛选抗恰加斯病新药的应用

Reporter genes and transgenic (Kinetoplastida, Trypanosomatidae): applications for screening new drugs against Chagas disease.

作者信息

de Sousa Oliveira Daniele Santana, da Silva Elis Dionisio, Galvão Júnior Fábio Farias, Moura Danielle Maria Nascimento, Sales-Junior Policarpo Ademar, Brelaz-de-Castro Maria Carolina Accioly, Pereira Valéria Rêgo Alves

机构信息

Postgraduation Program in Therapeutic Innovation, Federal University of Pernambuco, Recife, Pernambuco, Brazil.

Health and Biotechnology Institute, Federal University of Amazonas, Coari, Amazonas, Brazil.

出版信息

Front Med (Lausanne). 2025 May 20;12:1591148. doi: 10.3389/fmed.2025.1591148. eCollection 2025.

DOI:10.3389/fmed.2025.1591148
PMID:40463976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12129773/
Abstract

Chagas disease is considered a public health issue, especially in Latin America. To this date, the course of the infection caused by the parasite is yet to be completely understood and the conventional treatment do not promote a cure in the chronic phase, meaning there is an urgent need to discover new drugs. The expression of reporter genes by transgenic parasites has become an important tool in the screening of new compounds, whether in the study of the parasite, in the development of and assays, or in the application of High-Throughput Screening utilizing compounds collections. This review sought to gather information about transgenic applications in screening studies of compounds with action specifically against Chagas disease, the reporter genes in use, besides the highlighted characteristics of each one by the literature, including the performed assays, evolutionary forms and techniques applied, aiming to facilitate the identification of the reporter gene system or research model whose characteristics best adapt to the needs of new studies, contributing to the decisions about a framework adaptable to the reality of laboratories, in the screening of potentially trypanocidal compounds.

摘要

恰加斯病被视为一个公共卫生问题,尤其是在拉丁美洲。迄今为止,由该寄生虫引起的感染病程尚未完全明了,传统治疗方法无法治愈慢性期感染,这意味着迫切需要发现新药物。转基因寄生虫表达报告基因已成为筛选新化合物的重要工具,无论是在寄生虫研究、检测方法的开发与应用中,还是在利用化合物库进行的高通量筛选中。本综述旨在收集有关转基因在筛选对恰加斯病有特效作用的化合物的研究中的应用信息、所使用的报告基因,以及文献中突出的每种报告基因的特征,包括所进行的检测、进化形式和应用的技术,旨在便于识别其特征最适合新研究需求的报告基因系统或研究模型,为筛选潜在杀锥虫化合物时有关适用于实验室实际情况的框架的决策提供帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e9/12129773/405b96655b5c/fmed-12-1591148-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e9/12129773/405b96655b5c/fmed-12-1591148-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e9/12129773/405b96655b5c/fmed-12-1591148-g001.jpg

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本文引用的文献

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Fighting Strategies Against Chagas' Disease: A Review.对抗恰加斯病的斗争策略:综述
Pathogens. 2025 Feb 12;14(2):183. doi: 10.3390/pathogens14020183.
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Clinical features of Chagas disease progression and severity.恰加斯病进展与严重程度的临床特征。
Lancet Reg Health Am. 2024 Sep 13;37:100832. doi: 10.1016/j.lana.2024.100832. eCollection 2024 Sep.
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A panel of phenotypically and genotypically diverse bioluminescent:fluorescent Trypanosoma cruzi strains as a resource for Chagas disease research.一组表型和基因型多样化的生物发光:荧光克氏锥虫菌株作为恰加斯病研究的资源。
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A versatile 2A peptide-based strategy for ectopic expression and endogenous gene tagging in .一种基于2A肽的通用策略,用于在……中进行异位表达和内源基因标记。
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Clinical trials for Chagas disease: etiological and pathophysiological treatment.恰加斯病的临床试验:病因学和病理生理学治疗
Front Microbiol. 2023 Dec 15;14:1295017. doi: 10.3389/fmicb.2023.1295017. eCollection 2023.
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The Intracellular Amastigote of Trypanosoma cruzi Maintains an Actively Beating Flagellum.克氏锥虫的内阿米巴滋养体维持着活跃的鞭毛摆动。
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Reporter gene systems: A powerful tool for studies.报告基因系统:研究的强大工具。
Curr Res Microb Sci. 2022 Sep 29;3:100165. doi: 10.1016/j.crmicr.2022.100165. eCollection 2022.
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Past and future of trypanosomatids high-throughput phenotypic screening.无。
Mem Inst Oswaldo Cruz. 2022 Mar 11;117:e210402. doi: 10.1590/0074-02760210402. eCollection 2022.
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Perspectives for a new drug candidate for Chagas disease therapy.用于恰加斯病治疗的新药候选药物的展望。
Mem Inst Oswaldo Cruz. 2022 Mar 14;117:e220004. doi: 10.1590/0074-02760220004. eCollection 2022.
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Live-imaging rate-of-kill compound profiling for Chagas disease drug discovery with a new automated high-content assay.利用新的自动化高通量检测方法对克氏锥虫病药物发现进行实时杀伤化合物分析。
PLoS Negl Trop Dis. 2021 Oct 11;15(10):e0009870. doi: 10.1371/journal.pntd.0009870. eCollection 2021 Oct.