病毒趋向性的分子工程

Molecular Engineering of Virus Tropism.

机构信息

Viral Vector Core, Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

出版信息

Int J Mol Sci. 2024 Oct 15;25(20):11094. doi: 10.3390/ijms252011094.

Abstract

Engineered viral vectors designed to deliver genetic material to specific targets offer significant potential for disease treatment, safer vaccine development, and the creation of novel biochemical research tools. Viral tropism, the specificity of a virus for infecting a particular host, is often modified in recombinant viruses to achieve precise delivery, minimize off-target effects, enhance transduction efficiency, and improve safety. Key factors influencing tropism include surface protein interactions between the virus and host-cell, the availability of host-cell machinery for viral replication, and the host immune response. This review explores current strategies for modifying the tropism of recombinant viruses by altering their surface proteins. We provide an overview of recent advancements in targeting non-enveloped viruses (adenovirus and adeno-associated virus) and enveloped viruses (retro/lentivirus, Rabies, Vesicular Stomatitis Virus, and Herpesvirus) to specific cell types. Additionally, we discuss approaches, such as rational design, directed evolution, and in silico and machine learning-based methods, for generating novel AAV variants with the desired tropism and the use of chimeric envelope proteins for pseudotyping enveloped viruses. Finally, we highlight the applications of these advancements and discuss the challenges and future directions in engineering viral tropism.

摘要

经工程改造的病毒载体旨在将遗传物质递送到特定靶标,为疾病治疗、更安全的疫苗开发和新型生化研究工具的创造提供了巨大潜力。病毒的嗜性,即病毒感染特定宿主的特异性,通常在重组病毒中被修饰,以实现精确的递药、最小化脱靶效应、提高转导效率和提高安全性。影响嗜性的关键因素包括病毒与宿主细胞之间的表面蛋白相互作用、病毒复制所需的宿主细胞机制的可用性以及宿主免疫反应。本综述探讨了通过改变表面蛋白来修饰重组病毒嗜性的当前策略。我们提供了针对特定细胞类型的非包膜病毒(腺病毒和腺相关病毒)和包膜病毒(逆转录病毒/慢病毒、狂犬病病毒、水疱性口炎病毒和疱疹病毒)的靶向最新进展概述。此外,我们还讨论了用于生成具有所需嗜性的新型 AAV 变体的方法,如理性设计、定向进化以及基于计算和机器学习的方法,以及用于包膜病毒假型化的嵌合包膜蛋白。最后,我们强调了这些进展的应用,并讨论了工程病毒嗜性方面的挑战和未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6119/11508178/da70566c521e/ijms-25-11094-g001.jpg

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