Flexible nano-liposomes-encapsulated recombinant UL8-siRNA (r/si-UL8) based on bioengineering strategy inhibits herpes simplex virus-1 infection

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2024-06-21 DOI:10.1016/j.antiviral.2024.105936

Jiawei Pei , Ye Tian , Yamei Dang , Wei Ye , Xiaoqian Liu , Ningbo Zhao , Jiangfan Han , Yongheng Yang , Ziqing Zhou , Xudong Zhu , Hao Zhang , Arshad Ali , Yu Li , Fanglin Zhang , Yingfeng Lei , Airong Qian

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引用次数: 0

Abstract

Herpes simplex virus-1 (HSV-1) infection can cause various diseases and the current therapeutics have limited efficacy. Small interfering RNA (siRNA) therapeutics are a promising approach against infectious diseases by targeting the viral mRNAs directly. Recently, we employed a novel tRNA scaffold to produce recombinant siRNA agents with few natural posttranscriptional modifications. In this study, we aimed to develop a specific prodrug against HSV-1 infection based on siRNA therapeutics by bioengineering technology. We screened and found that UL8 of the HSV-1 genome was an ideal antiviral target based on RNAi. Next, we used a novel bio-engineering approach to manufacture recombinant UL8-siRNA (r/si-UL8) in Escherichia coli with high purity and activity. The r/si-UL8 was selectively processed to mature si-UL8 and significantly reduced the number of infectious virions in human cells. r/si-UL8 delivered by flexible nano-liposomes significantly decreased the viral load in the skin and improved the survival rate in the preventive mouse zosteriform model. Furthermore, r/si-UL8 also effectively inhibited HSV-1 infection in a 3D human epidermal skin model. Taken together, our results highlight that the novel siRNA bioengineering technology is a unique addition to the conventional approach for siRNA therapeutics and r/si-UL8 may be a promising prodrug for curing HSV-1 infection.

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基于生物工程策略的柔性纳米脂质体包裹重组 UL8-siRNA (r/si-UL8) 可抑制单纯疱疹病毒-1 感染。

单纯疱疹病毒-1（HSV-1）感染可导致多种疾病，而目前的疗法疗效有限。小干扰 RNA（siRNA）疗法可直接靶向病毒 mRNA，是一种治疗传染性疾病的有效方法。最近，我们采用了一种新型 tRNA 支架来生产重组 siRNA 制剂，其转录后修饰很少。本研究旨在通过生物工程技术，开发一种基于 siRNA 疗法的抗 HSV-1 感染的特异性原药。我们筛选发现，HSV-1 基因组的 UL8 是基于 RNAi 的理想抗病毒靶点。接下来，我们采用一种新颖的生物工程方法，在大肠杆菌中制造出了高纯度、高活性的重组 UL8-siRNA（r/si-UL8）。通过柔性纳米脂质体递送的 r/si-UL8 能显著降低皮肤中的病毒载量，提高预防性小鼠带状疱疹模型的存活率。此外，r/si-UL8 还能有效抑制三维人体表皮模型中的 HSV-1 感染。综上所述，我们的研究结果表明，新型 siRNA 生物工程技术是对传统 siRNA 治疗方法的一种独特补充，r/si-UL8 可能是一种治疗 HSV-1 感染的有效药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.