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From Enemies to Friends: Converting Disease-Causing Viruses to Therapeutic Tools
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From Enemies to Friends: Converting Disease-Causing Viruses to Therapeutic Tools

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Viral Genomics".

Deadline for manuscript submissions: closed (10 March 2023) | Viewed by 7467

Special Issue Editors

Dr. Wenli Zhang

E-Mail Website
Guest Editor
Virology and Microbiology, Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, Germany
Interests: adenovirus; vectorization; recombinant virus; viral vector; virotherapy
Prof. Dr. Anja Ehrhardt

E-Mail Website
Guest Editor
Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, Germany
Interests: viruses; adenovirus; vectorization; gene therapy; oncolytic viral therapy; genome editing

Special Issue Information

Dear Colleagues,

The conversion of wild-type viruses into therapeutic vectors represents a remarkable milestone in virology that has been achieved in the past decades. Virologists have reconstructed and fine-tuned their enemies (disease-causing viruses) to therapeutic tools to fight diseases. For examples, adenoviruses are currently used as vaccine vectors to combat the severe acute respiratory syndrome (SARS) CoV-2 pandemic, several AAV- and lentivirus-based gene therapy products are already on the market, and many viruses are being investigated as oncolytic/immune therapy platforms, such as herpes simplex virus-based talimogene laherparepvec (T-VEC).

Transforming viruses from enemies to friends remains challenging in many aspects, such as the deep understanding of basic virology, the proper methods for molecular engineering and the establishment of suitable vector systems. The previous accumulated knowledge has enabled us to generate powerful viral vector tools, while novel scientific and technical advancements will help us to further improve these vectors. Therefore, we believe it is important to prepare a Special Issue with the title “From enemies to friends: converting disease-causing viruses to therapeutic tools”.

We are pleased to invite colleges from different virus fields to contribute to our Special Issue. We welcome the submission of expert reviews on individual viruses to summarize the basic principles as well as current progress on the adaptation, attenuation and engineering of viral vectors, as well as current original research works.

Dr. Wenli Zhang
Prof. Dr. Anja Ehrhardt
Guest Editors

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. Genes 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.

Keywords

  • virus genome/gene
  • vectorization
  • viral genome engineering
  • gene/transgene function and design
  • vaccine vectors
  • gene therapy tools
  • oncolytic viruses

Published Papers (4 papers)

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Research

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17 pages, 2240 KiB  
Article
CELO Fiber1 Knob Is a Promising Candidate to Modify the Tropism of Adenoviral Vectors
by Yangyang Sun, Xiaohui Zou, Xiaojuan Guo, Chunlei Yang, Tao Hung and Zhuozhuang Lu
Genes 2022, 13(12), 2316; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13122316 - 8 Dec 2022
Cited by 2 | Viewed by 1295
Abstract
Fowl adenovirus 4 (FAdV-4) has the potential to be constructed as a gene transfer vector for human gene therapy or vaccine development to avoid the pre-existing immunity to human adenoviruses. To enhance the transduction of FAdV-4 to human cells, CELO fiber1 knob (CF1K) [...] Read more.
Fowl adenovirus 4 (FAdV-4) has the potential to be constructed as a gene transfer vector for human gene therapy or vaccine development to avoid the pre-existing immunity to human adenoviruses. To enhance the transduction of FAdV-4 to human cells, CELO fiber1 knob (CF1K) was chosen to replace the fiber2 knob in FAdV-4 to generate recombinant virus F2CF1K-CG. The original FAdV4-CG virus transduced 4% human 293 or 1% HEp-2 cells at the multiplicity of infection of 1000 viral particles per cell. In contrast, F2CF1K-CG could transduce 98% 293 or 60% HEp-2 cells under the same conditions. Prokaryotically expressed CF1K protein blocked 50% transduction of F2CF1K-CG to 293 cells at a concentration of 1.3 µg/mL while it only slightly inhibited the infection of human adenovirus 5 (HAdV-5), suggesting CF1K could bind to human cells in a manner different from HAdV-5 fiber. The incorporation of CF1K had no negative effect on the growth of FAdV-4 in the packaging cells. In addition, CF1K-pseudotyped HAdV-41 could transduce HEp-2 and A549 cells more efficiently. These data indicated that CF1K had the priority to be considered when there is a need to modify adenovirus tropism. Full article
(This article belongs to the Special Issue From Enemies to Friends: Converting Disease-Causing Viruses to Therapeutic Tools)
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16 pages, 3147 KiB  
Article
Role of Fiber Shaft Length in Tumor Targeting with Ad5/3 Vectors
by Maximilian Richter, Hongjie Wang and André Lieber
Genes 2022, 13(11), 2056; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13112056 - 7 Nov 2022
Viewed by 1607
Abstract
Desmoglein 2 (DSG2) is overexpressed in many epithelial cancers and therefore represents a target receptor for oncolytic viruses, including Ad5/3-based viruses. For most Ad serotypes, the receptor-binding fiber is composed of tail, shaft, and knob domains. Here, we investigated the role of the [...] Read more.
Desmoglein 2 (DSG2) is overexpressed in many epithelial cancers and therefore represents a target receptor for oncolytic viruses, including Ad5/3-based viruses. For most Ad serotypes, the receptor-binding fiber is composed of tail, shaft, and knob domains. Here, we investigated the role of the fiber shaft in Ad5/3 tumor transduction in vitro and in human DSG2-transgenic mice carrying human DSG2high tumors. DSG2tg mice express DSG2 in a pattern similar to humans. We constructed Ad5/3L (with the “long” Ad5 shaft) and Ad5/3S (with the “short” Ad3 shaft) expressing GFP or luciferase. In in vitro studies we found that coagulation factor X, which is known to mediate undesired hepatocyte transduction of Ad5, enhances the transduction of Ad5/3(L), but not the transduction of Ad5/3(S). We therefore hypothesized that Ad5/3(S) would target DSG2high tumors while sparing the liver after intravenous injection. In vivo imaging studies for luciferase and analysis of luciferase activity in isolated organs, showed that Ad5/3(L) vectors efficiently transduced DSG2high tumors and liver but not normal epithelial tissues after intravenous injection. Ad5/3(S) showed minimal liver transduction, however it failed to transduce DSG2high tumors. Further modifications of the Ad5/3(S) capsid are required to compensate for the lower infectivity of Ad5/3(S) vectors. Full article
(This article belongs to the Special Issue From Enemies to Friends: Converting Disease-Causing Viruses to Therapeutic Tools)
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Review

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11 pages, 576 KiB  
Review
Adenoviral Vectors: Potential as Anti-HBV Vaccines and Therapeutics
by Tasneem Farhad, Keila Neves, Patrick Arbuthnot and Mohube Betty Maepa
Genes 2022, 13(11), 1941; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13111941 - 25 Oct 2022
Cited by 4 | Viewed by 1896
Abstract
Adenoviral vaccines have been at the front line in the fight against pandemics caused by viral infections such as Ebola and the coronavirus disease 2019. This has revived an interest in developing these vectors as vaccines and therapies against other viruses of health [...] Read more.
Adenoviral vaccines have been at the front line in the fight against pandemics caused by viral infections such as Ebola and the coronavirus disease 2019. This has revived an interest in developing these vectors as vaccines and therapies against other viruses of health importance such as hepatitis B virus (HBV). Current hepatitis B therapies are not curative; hence, chronic hepatitis B remains the major risk factor for development of liver disease and death in HBV-infected individuals. The ability to induce a robust immune response and high liver transduction efficiency makes adenoviral vectors attractive tools for anti-HBV vaccine and therapy development, respectively. This review describes recent developments in designing adenoviral-vector-based therapeutics and vaccines against HBV infection. Full article
(This article belongs to the Special Issue From Enemies to Friends: Converting Disease-Causing Viruses to Therapeutic Tools)
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Other

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17 pages, 15203 KiB  
Protocol
HEHR: Homing Endonuclease-Mediated Homologous Recombination for Efficient Adenovirus Genome Engineering
by Katrin Schröer, Fatima Arakrak, Annika Bremke, Anja Ehrhardt and Wenli Zhang
Genes 2022, 13(11), 2129; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13112129 - 16 Nov 2022
Cited by 2 | Viewed by 2075
Abstract
Adenoviruses are non-enveloped linear double-stranded DNA viruses with over 100 types in humans. Adenovirus vectors have gained tremendous attention as gene delivery vehicles, as vaccine vectors and as oncolytic viruses. Although various methods have been used to generate adenoviral vectors, the vector-producing process [...] Read more.
Adenoviruses are non-enveloped linear double-stranded DNA viruses with over 100 types in humans. Adenovirus vectors have gained tremendous attention as gene delivery vehicles, as vaccine vectors and as oncolytic viruses. Although various methods have been used to generate adenoviral vectors, the vector-producing process remains technically challenging regarding efficacious genome modification. Based on our previously reported adenoviral genome modification streamline via linear–circular homologous recombination, we further develop an HEHR (combining Homing Endonucleases and Homologous Recombination) method to engineer adenoviral genomes more efficiently. I-PpoI, a rare endonuclease encoded by a group I intron, was introduced into the previously described ccdB counter-selection marker. We found that the I-PpoI pre-treatment of counter-selection containing parental plasmid increased the homologous recombination efficiency up to 100%. The flanking of the counter-selection marker with either single or double I-PpoI sites showed enhanced efficacy. In addition, we constructed a third counter-selection marker flanked by an alternative restriction enzyme: AbsI, which could be applied in case the I-PpoI site already existed in the transgene cassette that was previously inserted in the adenovirus genome. Together, HEHR can be applied for seamless sequence replacements, deletions and insertions. The advantages of HEHR in seamless mutagenesis will facilitate rational design of adenoviral vectors for diverse purposes. Full article
(This article belongs to the Special Issue From Enemies to Friends: Converting Disease-Causing Viruses to Therapeutic Tools)
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