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靶向与吸血蝙蝠相关的狂犬病病毒磷蛋白mRNA的短干扰RNA。

Short interfering RNAs targeting a vampire-bat related rabies virus phosphoprotein mRNA.

作者信息

Ono Ekaterina Alexandrovna Durymanova, Taniwaki Sueli Akemi, Brandão Paulo

机构信息

University of São Paulo, School of Veterinary Medicine, Department of Preventive Veterinary Medicine and Animal Health, São Paulo, Brazil.

University of São Paulo, School of Veterinary Medicine, Department of Preventive Veterinary Medicine and Animal Health, São Paulo, Brazil.

出版信息

Braz J Microbiol. 2017 Jul-Sep;48(3):566-569. doi: 10.1016/j.bjm.2016.11.007. Epub 2017 Feb 5.

Abstract

The aim of this study was to assess the in vitro and in vivo effects of short-interfering RNAs (siRNAs) against rabies virus phosphoprotein (P) mRNA in a post-infection treatment for rabies as an extension of a previous report (Braz J Microbiol. 2013 Nov 15;44(3):879-82). To this end, rabies virus strain RABV-4005 (related to the Desmodus rotundus vampire bat) were used to inoculate BHK-21 cells and mice, and the transfection with each of the siRNAs was made with Lipofectamine-2000™. In vitro results showed that siRNA 360 was able to inhibit the replication of strain RABV-4005 with a 1log decrease in virus titter and 5.16-fold reduction in P mRNA, 24h post-inoculation when compared to non-treated cells. In vivo, siRNA 360 was able to induce partial protection, but with no significant difference when compared to non-treated mice. These results indicate that, despite the need for improvement for in vivo applications, P mRNA might be a target for an RNAi-based treatment for rabies.

摘要

本研究的目的是评估针对狂犬病病毒磷蛋白(P)mRNA的短干扰RNA(siRNA)在狂犬病感染后治疗中的体外和体内效果,作为先前报告(《巴西微生物学杂志》。2013年11月15日;44(3):879 - 82)的延伸。为此,使用狂犬病病毒株RABV - 4005(与吸血蝙蝠圆叶蝠相关)接种BHK - 21细胞和小鼠,并使用Lipofectamine - 2000™对每种siRNA进行转染。体外结果显示,与未处理的细胞相比,接种后24小时,siRNA 360能够抑制RABV - 4005株的复制,病毒滴度下降1个对数,P mRNA减少5.16倍。在体内,siRNA 360能够诱导部分保护,但与未处理的小鼠相比无显著差异。这些结果表明,尽管体内应用需要改进,但P mRNA可能是基于RNAi的狂犬病治疗的一个靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dab/5498410/4922f89b6207/gr1.jpg

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