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

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

  • Antiviral Res. 2024 Aug:228:105936. doi: 10.1016/j.antiviral.2024.105936.
Jiawei Pei 1,  Ye Tian 2,  Yamei Dang 3,  Wei Ye 3,  Xiaoqian Liu 3,  Ningbo Zhao 3,  Jiangfan Han 2,  Yongheng Yang 3,  Ziqing Zhou 3,  Xudong Zhu 3,  Hao Zhang 2,  Arshad Ali 4,  Yu Li 5,  Fanglin Zhang 3,  Yingfeng Lei 3,  Airong Qian 6
Affiliations

Affiliations

  • 1 Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, Northwestern Polytechnical University, Xi'an, 710072, China; Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: peijiawei@mail.nwpu.edu.cn.
  • 2 Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, Northwestern Polytechnical University, Xi'an, 710072, China.
  • 3 Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 4 GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, China.
  • 5 Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
  • 6 Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, Northwestern Polytechnical University, Xi'an, 710072, China. Electronic address: qianair@nwpu.edu.cn.
PMID: 38908520 DOI: 10.1016/j.antiviral.2024.105936
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.

Keywords

Herpes simplex virus-1 (HSV-1); Recombinant siRNA; SiRNA therapeutic; r/si-UL8.

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