Self-Replicating RNA Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 5351

Special Issue Editor


E-Mail Website
Guest Editor
PanTherapeutics, Rue des Remparts 4, CH-1095 Lutry, Switzerland
Interests: viral gene therapy; viral vaccines; gene expression using viral vectors; structural biology; epigenetics; nutrigenomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Self-replicating RNA viruses possess a special feature of massive self-amplification of viral RNA in a broad range of mammalian and non-mammalian host cells, providing a high-level expression of heterologous genes. However, the expression is transient due to the non-integrating, rapidly degrading viral RNA genome. For this reason, self-replicating RNA viruses have been ideal for the prevention and therapy of infectious diseases and various cancers. In contrast, self-replicating RNA viruses are not suitable for the treatment of chronic diseases requiring long-term transgene expression. Among self-replicating RNA viruses, alphaviruses and flaviviruses possessing a single-stranded RNA genome of positive polarity have been frequently used. Likewise, the negative-stranded measles viruses and rhabdoviruses have also been utilized. Self-replicating RNA viruses have elicited robust target-specific immune responses and provided protection against challenges with infectious agents in preclinical animal studies. Moreover, immunization studies have demonstrated tumor-associated antigen-specific immune responses and protection against tumor challenges in animal tumor models. In a limited number of clinical trials, good safety and tolerability have been demonstrated in cancer patients although therapeutic efficacy needs to be improved through vector and dose optimization. Self-replicating RNA viruses possess wide flexibility as delivery vectors can be utilized as recombinant viral particles, RNA replicons or DNA replicons. Due to the RNA self-amplification, RNA replicons are superior to synthetic mRNA, meaning that similar immune response and protection can be achieved by using 100–1000-fold-lower RNA doses. Similarly, DNA replicons doses can be significantly reduced compared to conventional plasmid DNA. In the case of cancer therapy, oncolytic RNA viruses have demonstrated tumor-cell-specific replication leading to efficient tumor cell killing without causing harm to normal tissue. In summary, there is a huge potential of using self-replicating RNA viruses for the prevention and treatment of infectious diseases and various cancers.

Dr. Kenneth Lundstrom
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Review

14 pages, 501 KiB  
Review
Self-Replicating Alphaviruses: From Pathogens to Therapeutic Agents
by Kenneth Lundstrom
Viruses 2024, 16(11), 1762; https://doi.org/10.3390/v16111762 - 12 Nov 2024
Viewed by 901
Abstract
Alphaviruses are known for being model viruses for studying cellular functions related to viral infections 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 [...] Read more.
Alphaviruses are known for being model viruses for studying cellular functions related to viral infections 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. 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 can provide higher translational efficiency and eliminate interference with cellular translation. 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 along with protection against challenges with lethal doses of infectious agents in rodents and primates. Similarly, the expression of anti-tumor genes and immunostimulatory genes from alphavirus vectors has provided tumor growth inhibition, tumor regression, and cures in animal cancer models. Moreover, protection against tumor challenges has been observed. In clinical settings, patient benefits have been reported. Alphaviruses have also been considered for the treatment of neurological disorders due to their neurotrophic preference. Full article
(This article belongs to the Special Issue Self-Replicating RNA Viruses)
Show Figures

Figure 1

17 pages, 1407 KiB  
Review
Trans-Amplifying RNA: A Journey from Alphavirus Research to Future Vaccines
by Ayşegül Yıldız, Cristian Răileanu and Tim Beissert
Viruses 2024, 16(4), 503; https://doi.org/10.3390/v16040503 - 25 Mar 2024
Cited by 3 | Viewed by 3897
Abstract
Replicating RNA, including self-amplifying RNA (saRNA) and trans-amplifying RNA (taRNA), holds great potential for advancing the next generation of RNA-based vaccines. Unlike in vitro transcribed mRNA found in most current RNA vaccines, saRNA or taRNA can be massively replicated within cells in the [...] Read more.
Replicating RNA, including self-amplifying RNA (saRNA) and trans-amplifying RNA (taRNA), holds great potential for advancing the next generation of RNA-based vaccines. Unlike in vitro transcribed mRNA found in most current RNA vaccines, saRNA or taRNA can be massively replicated within cells in the presence of RNA-amplifying enzymes known as replicases. We recently demonstrated that this property could enhance immune responses with minimal injected RNA amounts. In saRNA-based vaccines, replicase and antigens are encoded on the same mRNA molecule, resulting in very long RNA sequences, which poses significant challenges in production, delivery, and stability. In taRNA-based vaccines, these challenges can be overcome by splitting the replication system into two parts: one that encodes replicase and the other that encodes a short antigen-encoding RNA called transreplicon. Here, we review the identification and use of transreplicon RNA in alphavirus research, with a focus on the development of novel taRNA technology as a state-of-the art vaccine platform. Additionally, we discuss remaining challenges essential to the clinical application and highlight the potential benefits related to the unique properties of this future vaccine platform. Full article
(This article belongs to the Special Issue Self-Replicating RNA Viruses)
Show Figures

Figure 1

Back to TopTop