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Virus Engineering and Applications: 3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 637

Special Issue Editor


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Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy
Interests: oncolytic herpes simplex virus; tropism retargeting; cancer receptors; virus engineering; virus arming; virus-mediated transgene expression
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Special Issue Information

Dear Colleagues,

The recent SARS-CoV-2 pandemic recalled and focused worldwide attention, perception, and awareness on viruses and highlighted the global need to prepare for future emerging threats. At present, this is just the most exposed facet of the virus world. However, viruses are much more. Virus engineering is a well-established discipline, both as a tool and as a research subject, and it is now receiving attention at the intersection with novel, expanding omics breakthroughs. Thus, the possibility to retrieve viral sequences from the most diverse matrices expanded the boundaries of the virosphere in an unprecedented way. Here, virus engineering comes into play, allowing for the study of the biological properties of viral entities, or just the parts thereof, that have not been isolated as particles or whose host is not known, with tremendous implications both in ecology and global health. Virus engineering allows for reviving both known extinct or unknown possible pathogens, variants of concern, etc., and designing and devising countermeasures, drugs, or vaccines, with a constant eye on ethics and safety issues. Virus engineering allows for shedding light on virus origin, emergence, and evolution as well. Finally, an ever-growing body of knowledge builds up for increasingly sophisticated viruses engineered as therapeutic platforms themselves, for gene therapy, oncolytic virotherapy, or bio-nanomaterials. In this regard, submissions of original research papers, perspectives, and reviews are welcome for this Special Issue. Topics of interest include, but are not limited to:

  • Basic virology;
  • Viral biotechnology;
  • Virus engineering platforms, toolboxes, and technologies;
  • Viral vaccine platforms;
  • Viral gene therapy;
  • Oncolytic virotherapy and immunovirotherapy;
  • Personalized medicine with virus-based biologicals;
  • Ethics of virus engineering;
  • Virus origin, emergence, and evolution;
  • Viral synthetic biology;
  • Virus metagenomics and the virosphere;
  • Virus-based bio-nanomaterials and bio-nanotechnologies.

Dr. Laura Menotti
Guest Editor

Manuscript Submission Information

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Keywords

  • virus engineering
  • oncolytic virotherapy
  • immunovirotherapy
  • viral biotechnology

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Published Papers (1 paper)

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Research

28 pages, 11739 KiB  
Article
Development and Characterization of an Oncolytic Human Adenovirus-Based Vector Co-Expressing the Adenovirus Death Protein and p14 Fusion-Associated Small Transmembrane Fusogenic Protein
by Kathy L. Poulin, Ryan G. Clarkin, Joshua Del Papa and Robin J. Parks
Int. J. Mol. Sci. 2024, 25(22), 12451; https://doi.org/10.3390/ijms252212451 - 20 Nov 2024
Viewed by 553
Abstract
Human adenovirus (HAdV)-based oncolytic vectors, which are designed to preferentially replicate in and kill cancer cells, have shown modest efficacy in human clinical trials in part due to poor viral distribution throughout the tumor mass. Previously, we showed that expression of the p14 [...] Read more.
Human adenovirus (HAdV)-based oncolytic vectors, which are designed to preferentially replicate in and kill cancer cells, have shown modest efficacy in human clinical trials in part due to poor viral distribution throughout the tumor mass. Previously, we showed that expression of the p14 fusion-associated small transmembrane (FAST) fusogenic protein could enhance oncolytic HAdV efficacy and reduce tumor growth rate in a human xenograft mouse model of cancer. We now explore whether co-expression of the adenovirus death protein (ADP) with p14 FAST protein could synergize to further enhance oncolytic vector efficacy. ADP is naturally encoded within the early region 3 (E3) of HAdV, a region which is frequently removed from HAdV-based vectors, and functions to enhance cell lysis and progeny release. We evaluated a variety of approaches to achieve optimal expression of the two proteins, the most efficient method being insertion of an expression cassette within the E3 deletion, consisting of the coding sequences for p14 FAST protein and ADP separated by a self-cleaving peptide derived from the porcine teschovirus-1 (P2A). However, the quantities of p14 FAST protein and ADP produced from this vector were reduced approximately 10-fold compared to a similar vector-expressing only p14 FAST protein and wildtype HAdV, respectively. Compared to our original oncolytic vector-expressing p14 FAST protein alone, reduced expression of p14 FAST protein and ADP from the P2A construct reduced cell-cell fusion, vector spread, and cell-killing activity in human A549 adenocarcinoma cells in culture. These studies show that a self-cleaving peptide can be used to express two different transgenes in an armed oncolytic HAdV vector, but also highlight the challenges in maintaining adequate transgene expression when modifying vector design. Full article
(This article belongs to the Special Issue Virus Engineering and Applications: 3rd Edition)
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