Preprint Review Version 1 This version is not peer-reviewed

Self-Replicating Alphaviruses: From Pathogens to Therapeutic Agents

Version 1 : Received: 14 October 2024 / Approved: 15 October 2024 / Online: 16 October 2024 (04:33:30 CEST)

How to cite: Lundstrom, K. Self-Replicating Alphaviruses: From Pathogens to Therapeutic Agents. Preprints 2024, 2024101186. https://doi.org/10.20944/preprints202410.1186.v1 Lundstrom, K. Self-Replicating Alphaviruses: From Pathogens to Therapeutic Agents. Preprints 2024, 2024101186. https://doi.org/10.20944/preprints202410.1186.v1

Abstract

Alphaviruses are known for being model viruses for studying cellular functions related to viral infection but also for causing epidemics in different parts of the world. More recently, alphavirus-based expression systems have demonstrated efficacy as vaccines against infectious diseases and as therapeutic applications for different cancers. The self-replicating feature of alphaviruses has provided the advantage of extremely high transgene expression of vaccine-related antigens and therapeutic anti-tumor and immunostimulatory genes, which has also permitted significantly reduced doses for prophylactic and therapeutic applications potentially reducing adverse events. Furthermore, alphaviruses have shown favorable flexibility as they can be delivered as recombinant viral particles, RNA replicons or DNA replicon-based plasmids. In the context of infectious diseases robust immune responses against the surface proteins of target agents have been observed and protection against challenges with lethal doses of infectious agents in rodents and primates. Similarly, expression of anti-tumor genes and immunostimulatory genes from alphavirus vectors has provided tumor growth inhibition, tumor regression and cure in animal cancer models. Moreover, protection against tumor challenges has been observed. In clinical settings, clinical benefits have been reported. Alphaviruses have also been considered for the treatment of neurological disorders due to their neurotrophic preference. Attention has been paid to alphavirus vector and expression system improvement. Point mutations in the non-structural alphaviral replicase genes have generated enhanced transgene expression and created temperature-sensitive expression vectors. The recently engineered trans-amplifying RNA system has facilitated vector production and enhanced the expression capacity.

Keywords

alphaviruses; viral particles; RNA replicons: DNA delivery; infectious diseases; cancer; vaccines; neurological disorders; therapy; clinical trials

Subject

Biology and Life Sciences, Virology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.