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Broad dengue neutralization in mosquitoes expressing an engineered antibody.
PLoS Pathogens ( IF 5.5 ) Pub Date : 2020-01-16 , DOI: 10.1371/journal.ppat.1008103
Anna Buchman , Stephanie Gamez , Ming Li , Igor Antoshechkin , Hsing-Han Li , Hsin-Wei Wang , Chun-Hong Chen , Melissa J. Klein , Jean-Bernard Duchemin , James E. Crowe , Prasad N. Paradkar , Omar S. Akbari

With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses.

中文翻译:

在表达工程抗体的蚊子中广泛中和登革热。

随着登革热病毒(DENV)在全球热带和亚热带地区流行,全球迫切需要有效的策略来控制传播这种疾病的蚊子。基因工程技术的最新进展使得创造出媒介能力降低的蚊子成为可能,从而限制了它们获取和传播病原体的能力。在这里,我们描述了经过综合改造以阻碍媒介对 DENV 的能力的埃及伊蚊的发育。这些蚊子表达编码源自广泛中和 DENV 人单克隆抗体的工程化单链可变片段的基因,并显着降低了所有四种主要抗原不同 DENV 血清型的病毒感染、传播和传播率。重要的是,这是第一个针对所有 DENV 血清型的工程方法,这对于有效抑制疾病至关重要。这些结果为开发有效的基于基因的 DENV 控制策略提供了一条令人信服的途径,该策略可以扩展到遏制其他虫媒病毒。
更新日期:2020-01-17
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