Research and Clinical Application of Adenovirus (AdV), Volume II

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 7260

Special Issue Editor


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Guest Editor
Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA
Interests: gene therapy approaches for cancer and non-malignant diseases; oncolytic adenovirus for cancer therapy and imaging; combination of virotherapy with radiation and chemotherapy; adenovirus-mediated immunotherapy for cancer; viral vectors as a tool for gene delivery
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Special Issue Information

Dear Colleagues,

The concept behind using viruses to fight human diseases is very straightforward: for millions of years, they have been delivering their genes to different types of mammalian and human cells. Indeed, virus-based gene therapy is a growing area of modern medicine as viruses have the potential to overcome the limitations of conventional therapeutic approaches.

Adenovirus (AdV) is one of the most versatile viral backbones with applications ranging from gene delivery and treatment of monogenic diseases to vaccination and cancer therapy. Adenoviruses can target a broad spectrum of both dividing and non-dividing cells, do not integrate into host DNA, have high in vivo transduction capacity, and are well characterized, thereby allowing for countless modifications of their genetic structure. The first AdV-based therapy took place in 1956, when 30 patients with cervical carcinoma were treated with adenoidal–pharyngeal–conjunctival virus, now known as an adenovirus. After a turbulent past full of both medical achievements and failures, the stigma related to adenovirus has been gradually replaced by the wide acceptance of the feasibility and safety of AdV-based therapeutics. It is difficult to overestimate the value of AdV during the COVID-19 pandemic as, to date, AdV represents the most effective viral vector platform for anti-SARS-CoV-2 vaccines. The recent clinical successes have also demonstrated the promise of tumor-selective, infectivity-improved oncolytic adenoviruses for cancer gene therapy and highlighted their role in inducing anticancer immunity.

In this second special issue, we discuss the latest advances in adenovirus research and how AdV can be used to treat human disease.

Dr. Julia Davydova
Guest Editor

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Keywords

  • adenovirus
  • gene
  • therapy
  • cancer
  • oncolytic
  • vaccine
  • delivery

Published Papers (4 papers)

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Research

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13 pages, 2321 KiB  
Article
DMSO and Its Role in Differentiation Impact Efficacy of Human Adenovirus (HAdV) Infection in HepaRG Cells
by Katharina Hofmann, Samuel Hofmann, Franziska Weigl, Julia Mai and Sabrina Schreiner
Viruses 2024, 16(4), 633; https://doi.org/10.3390/v16040633 - 19 Apr 2024
Viewed by 420
Abstract
Differentiated HepaRG cells are popular in vitro cell models for hepatotoxicity studies. Their differentiation is usually supported by the addition of dimethyl sulfoxide (DMSO), an amphipathic solvent widely used in biomedicine, for example, in potential novel therapeutic drugs and cryopreservation of oocytes. Recent [...] Read more.
Differentiated HepaRG cells are popular in vitro cell models for hepatotoxicity studies. Their differentiation is usually supported by the addition of dimethyl sulfoxide (DMSO), an amphipathic solvent widely used in biomedicine, for example, in potential novel therapeutic drugs and cryopreservation of oocytes. Recent studies have demonstrated drastic effects, especially on epigenetics and extracellular matrix composition, induced by DMSO, making its postulated inert character doubtful. In this work, the influence of DMSO and DMSO-mediated modulation of differentiation on human adenovirus (HAdV) infection of HepaRG cells was investigated. We observed an increase in infectivity of HepaRG cells by HAdVs in the presence of 1% DMSO. However, this effect was dependent on the type of medium used for cell cultivation, as cells in William’s E medium showed significantly stronger effects compared with those cultivated in DMEM. Using different DMSO concentrations, we proved that the impact of DMSO on infectability was dose-dependent. Infection of cells with a replication-deficient HAdV type demonstrated that the mode of action of DMSO was based on viral entry rather than on viral replication. Taken together, these results highlight the strong influence of the used cell-culture medium on the performed experiments as well as the impact of DMSO on infectivity of HepaRG cells by HAdVs. As this solvent is widely used in cell culture, those effects must be considered, especially in screening of new antiviral compounds. Full article
(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), Volume II)
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13 pages, 780 KiB  
Article
Effect of Human Adenovirus 36 on Response to Metformin Monotherapy in Obese Mexican Patients with Type 2 Diabetes: A Prospective Cohort Study
by José Carlos Tapia-Rivera, Héctor Eduardo Mendoza-Jaramillo, Christian Octavio González-Villaseñor, Mario Ramirez-Flores, José Alonso Aguilar-Velazquez, Andres López-Quintero, Edsaúl Emilio Pérez-Guerrero, María de los Ángeles Vargas-Rodriguez, Itzae Adonai Gutiérrez-Hurtado and Erika Martínez-López
Viruses 2023, 15(7), 1514; https://doi.org/10.3390/v15071514 - 07 Jul 2023
Cited by 1 | Viewed by 1993
Abstract
Human adenovirus 36 (HAdV-36) has been associated with obesity and changes in glucose and lipid metabolism. The virus has been reported to increase insulin sensitivity and paradoxically promote weight gain. Because of its effects on metabolism, infection with the virus could alter the [...] Read more.
Human adenovirus 36 (HAdV-36) has been associated with obesity and changes in glucose and lipid metabolism. The virus has been reported to increase insulin sensitivity and paradoxically promote weight gain. Because of its effects on metabolism, infection with the virus could alter the response to several drugs used to treat type 2 diabetes (DM2), such as metformin. The aim of this study was to test whether HAdV-36 affects the response to metformin in a group of obese patients with DM2. Methods: In a prospective cohort study, 103 obese patients with newly diagnosed DM2 were divided into two groups based on their HAdV-36 seropositivity (+HAdV-36 and −HAdV-36). Weight, glucose, cholesterol, triglycerides, body mass index, body fat percentage, and waist and hip circumference were measured and compared in both groups at baseline and after 45 days of metformin treatment. Results: Only glucose was significantly lower in the +HAdV-36 group at baseline, while all other variables were similar between the two study groups. After 45 days of follow-up, it was observed that the effect of metformin did not differ between the groups, but the variables improved significantly after treatment. Conclusions: In this study, we did not find that HAdV-36 had an effect on the response to metformin in obese patients with DM2. Full article
(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), Volume II)
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Review

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18 pages, 1966 KiB  
Review
Advances of Recombinant Adenoviral Vectors in Preclinical and Clinical Applications
by Luca Scarsella, Eric Ehrke-Schulz, Michael Paulussen, Serge C. Thal, Anja Ehrhardt and Malik Aydin
Viruses 2024, 16(3), 377; https://doi.org/10.3390/v16030377 - 28 Feb 2024
Viewed by 1073
Abstract
Adenoviruses (Ad) have the potential to induce severe infections in vulnerable patient groups. Therefore, understanding Ad biology and antiviral processes is important to comprehend the signaling cascades during an infection and to initiate appropriate diagnostic and therapeutic interventions. In addition, Ad vector-based vaccines [...] Read more.
Adenoviruses (Ad) have the potential to induce severe infections in vulnerable patient groups. Therefore, understanding Ad biology and antiviral processes is important to comprehend the signaling cascades during an infection and to initiate appropriate diagnostic and therapeutic interventions. In addition, Ad vector-based vaccines have revealed significant potential in generating robust immune protection and recombinant Ad vectors facilitate efficient gene transfer to treat genetic diseases and are used as oncolytic viruses to treat cancer. Continuous improvements in gene delivery capacity, coupled with advancements in production methods, have enabled widespread application in cancer therapy, vaccine development, and gene therapy on a large scale. This review provides a comprehensive overview of the virus biology, and several aspects of recombinant Ad vectors, as well as the development of Ad vector, are discussed. Moreover, we focus on those Ads that were used in preclinical and clinical applications including regenerative medicine, vaccine development, genome engineering, treatment of genetic diseases, and virotherapy in tumor treatment. Full article
(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), Volume II)
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38 pages, 2700 KiB  
Review
Evolving Horizons: Adenovirus Vectors’ Timeless Influence on Cancer, Gene Therapy and Vaccines
by Prasad D. Trivedi, Barry J. Byrne and Manuela Corti
Viruses 2023, 15(12), 2378; https://doi.org/10.3390/v15122378 - 03 Dec 2023
Cited by 2 | Viewed by 3172
Abstract
Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success of commercial oncolytic vector and multiple COVID-19 vaccines, adenovirus vectors are back in the spotlight. Adenovirus vectors can be used in gene therapy [...] Read more.
Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success of commercial oncolytic vector and multiple COVID-19 vaccines, adenovirus vectors are back in the spotlight. Adenovirus vectors can be used in gene therapy by altering the wild-type virus and making it replication-defective; specific viral genes can be removed and replaced with a segment that holds a therapeutic gene, and this vector can be used as delivery vehicle for tissue specific gene delivery. Modified conditionally replicative–oncolytic adenoviruses target tumors exclusively and have been studied in clinical trials extensively. This comprehensive review seeks to offer a summary of adenovirus vectors, exploring their characteristics, genetic enhancements, and diverse applications in clinical and preclinical settings. A significant emphasis is placed on their crucial role in advancing cancer therapy and the latest breakthroughs in vaccine clinical trials for various diseases. Additionally, we tackle current challenges and future avenues for optimizing adenovirus vectors, promising to open new frontiers in the fields of cell and gene therapies. Full article
(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), Volume II)
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