Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Molecular Engineering of Virus Tropism

Version 1 : Received: 19 September 2024 / Approved: 20 September 2024 / Online: 22 September 2024 (06:35:32 CEST)

How to cite: Martin, N. P.; He, B.; Wilson, B.; Chen, S.-H. Molecular Engineering of Virus Tropism. Preprints 2024, 2024091590. https://doi.org/10.20944/preprints202409.1590.v1 Martin, N. P.; He, B.; Wilson, B.; Chen, S.-H. Molecular Engineering of Virus Tropism. Preprints 2024, 2024091590. https://doi.org/10.20944/preprints202409.1590.v1

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 vi-rus) and enveloped viruses (Retro/Lentivirus, Rabies, Vesicular stomatitis virus, and Herpesvirus) to specific cell types. Additionally, we discuss approaches such as rational design, directed evo-lution, in silico and machine learning-based methods for generating novel AAV variants with 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.

Keywords

viral vectors; viral application; pseudotyping virus; virus envelope; virus envelope chimera; AAV serotype; AAV variant; capsid; AAV; lentivirus; retrovirus; g-deleted rabies virus; HSV

Subject

Biology and Life Sciences, Biology and Biotechnology

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