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Viruses
Special Issues
RNA Interference (RNAi) for Antiviral Therapy
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RNA Interference (RNAi) for Antiviral Therapy

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 21448

Special Issue Editor

Dr. Kenneth Lundstrom

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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,

The discovery of RNA interference (RNAi) has opened up completely new possibilities in research and therapeutic applications. In this context, small interfering RNAs (siRNAs) and micro-RNAs (miRNAs) are of particular interest. The attraction of therapeutic RNAi relates to its reversible nature, whereby an effective gene silencing the targeted RNA is degraded by a sequence-specific process, leaving no risk of prolonged effect after the termination of treatment. The delivery of RNAi has been considered to be one of the major obstacles for therapeutic efficacy and safety. For this reason, both non-viral and viral delivery methods for RNAi have been developed. The global threat of emerging lethal viral infectious diseases reaching epidemic levels has triggered the development of RNAi-based therapeutics. For example, RNAi approaches have been executed or planned for influenza virus, human immunodeficiency virus (HIV), hepatitis virus, Ebola virus, and Dengue virus. Clinical trials have been conducted for respiratory syncytial virus (RSV), hepatitis B virus (HBV), HIV, and Ebola virus. This Special Issue on RNAi for Antiviral Therapy aims at reviewing the recent progress in the field, from vector engineering and delivery technologies to clinical trials.

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.

Keywords

  • target identification
  • vector engineering
  • delivery
  • preclinical studies
  • clinical trials

Published Papers (5 papers)

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Editorial

Jump to: Research, Review

6 pages, 195 KiB  
Editorial
Are Viral Vectors Any Good for RNAi Antiviral Therapy?
by Kenneth Lundstrom
Viruses 2020, 12(10), 1189; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101189 - 20 Oct 2020
Cited by 7 | Viewed by 2988
Abstract
RNA interference (RNAi) represents a novel approach for alternative antiviral therapy. However, issues related to RNA delivery and stability have presented serious obstacles for obtaining good therapeutic efficacy. Viral vectors are capable of efficient delivery of RNAi as short interfering RNA (siRNA), short [...] Read more.
RNA interference (RNAi) represents a novel approach for alternative antiviral therapy. However, issues related to RNA delivery and stability have presented serious obstacles for obtaining good therapeutic efficacy. Viral vectors are capable of efficient delivery of RNAi as short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA). Efficacy in gene silencing for therapeutic applications against viral diseases has been demonstrated in various animal models. Rotavirus (RV) miR-7 can inhibit rotavirus replication by targeting the RV nonstructural protein 5. Viral gene silencing by targeting the RNAi pathway showed efficient suppression of hepatitis B virus replication by adeno-associated virus (AAV)-based delivery of RNAi hepatitis B virus (HBV) cassettes. Hepatitis C virus replication has been targeted by short hairpin RNA molecules expressed from lentivirus vectors. Potentially, RNAi-based approaches could be suitable for antiviral drugs against COVID-19. Full article
(This article belongs to the Special Issue RNA Interference (RNAi) for Antiviral Therapy)

Research

Jump to: Editorial, Review

21 pages, 3726 KiB  
Article
Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line
by Hossein M. Elbadawy, Mohi I. Mohammed Abdul, Naif Aljuhani, Adriana Vitiello, Francesco Ciccarese, Mohamed A. Shaker, Heba M. Eltahir, Giorgio Palù, Veronica Di Antonio, Hanieh Ghassabian, Claudia Del Vecchio, Cristiano Salata, Elisa Franchin, Eleonora Ponterio, Saleh Bahashwan, Khaled Thabet, Mekky M. Abouzied, Ahmed M. Shehata, Cristina Parolin, Arianna Calistri and Gualtiero Alvisiadd Show full author list remove Hide full author list
Viruses 2020, 12(9), 1044; https://0-doi-org.brum.beds.ac.uk/10.3390/v12091044 - 18 Sep 2020
Cited by 4 | Viewed by 3393
Abstract
Despite the introduction of directly acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, their cost, patient compliance, and viral resistance are still important issues to be considered. Here, we describe the generation of a novel JFH1-based HCV subgenomic replicon [...] Read more.
Despite the introduction of directly acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, their cost, patient compliance, and viral resistance are still important issues to be considered. Here, we describe the generation of a novel JFH1-based HCV subgenomic replicon double reporter cell line suitable for testing different antiviral drugs and therapeutic interventions. This cells line allowed a rapid and accurate quantification of cell growth/viability and HCV RNA replication, thus discriminating specific from unspecific antiviral effects caused by DAAs or cytotoxic compounds, respectively. By correlating cell number and virus replication, we could confirm the inhibitory effect on the latter of cell over confluency and characterize an array of lentiviral vectors expressing single, double, or triple cassettes containing different combinations of short hairpin (sh)RNAs, targeting both highly conserved viral genome sequences and cellular factors crucial for HCV replication. While all vectors were effective in reducing HCV replication, the ones targeting viral sequences displayed a stronger antiviral effect, without significant cytopathic effects. Such combinatorial platforms as well as the developed double reporter cell line might find application both in setting-up anti-HCV gene therapy approaches and in studies aimed at further dissecting the viral biology/pathogenesis of infection. Full article
(This article belongs to the Special Issue RNA Interference (RNAi) for Antiviral Therapy)
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17 pages, 9275 KiB  
Article
MicroRNA-7 Inhibits Rotavirus Replication by Targeting Viral NSP5 In Vivo and In Vitro
by Yan Zhou, Linlin Chen, Jing Du, Xiaoqing Hu, Yuping Xie, Jinyuan Wu, Xiaochen Lin, Na Yin, Maosheng Sun and Hongjun Li
Viruses 2020, 12(2), 209; https://0-doi-org.brum.beds.ac.uk/10.3390/v12020209 - 13 Feb 2020
Cited by 16 | Viewed by 2992
Abstract
Rotavirus (RV) is the major causes of severe diarrhea in infants and young children under five years of age. There are no effective drugs for the treatment of rotavirus in addition to preventive live attenuated vaccine. Recent evidence demonstrates that microRNAs (miRNAs) can [...] Read more.
Rotavirus (RV) is the major causes of severe diarrhea in infants and young children under five years of age. There are no effective drugs for the treatment of rotavirus in addition to preventive live attenuated vaccine. Recent evidence demonstrates that microRNAs (miRNAs) can affect RNA virus replication. However, the antiviral effect of miRNAs during rotavirus replication are largely unknown. Here, we determined that miR-7 is upregulated during RV replication and that it targets the RV NSP5 (Nonstructural protein 5). Results suggested that miR-7 affected viroplasm formation and inhibited RV replication by down-regulating RV NSP5 expression. Up-regulation of miR-7 expression is a common regulation method of different G-type RV-infected host cells. Then, we further revealed the antiviral effect of miR-7 in diarrhea suckling mice model. MiR-7 is able to inhibit rotavirus replication in vitro and in vivo. These data provide that understanding the role of cellular miR-7 during rotaviral replication may help in the identification of novel therapeutic small RNA molecule drug for anti-rotavirus. Full article
(This article belongs to the Special Issue RNA Interference (RNAi) for Antiviral Therapy)
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Review

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14 pages, 241 KiB  
Review
Viral Vectors Applied for RNAi-Based Antiviral Therapy
by Kenneth Lundstrom
Viruses 2020, 12(9), 924; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090924 - 23 Aug 2020
Cited by 18 | Viewed by 4576
Abstract
RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA) have demonstrated efficacy in gene silencing for therapeutic applications against viral diseases. Bioinformatics has played [...] Read more.
RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA) have demonstrated efficacy in gene silencing for therapeutic applications against viral diseases. Bioinformatics has played an important role in the design of efficient RNAi sequences targeting various pathogenic viruses. However, stability and delivery of RNAi molecules have presented serious obstacles for reaching therapeutic efficacy. For this reason, RNA modifications and formulation of nanoparticles have proven useful for non-viral delivery of RNAi molecules. On the other hand, utilization of viral vectors and particularly self-replicating RNA virus vectors can be considered as an attractive alternative. In this review, examples of antiviral therapy applying RNAi-based approaches in various animal models will be described. Due to the current coronavirus pandemic, a special emphasis will be dedicated to targeting Coronavirus Disease-19 (COVID-19). Full article
(This article belongs to the Special Issue RNA Interference (RNAi) for Antiviral Therapy)
20 pages, 983 KiB  
Review
Advances with RNAi-Based Therapy for Hepatitis B Virus Infection
by Fiona van den Berg, Shonisani Wendy Limani, Njabulo Mnyandu, Mohube Betty Maepa, Abdullah Ely and Patrick Arbuthnot
Viruses 2020, 12(8), 851; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080851 - 04 Aug 2020
Cited by 47 | Viewed by 6639
Abstract
Infection with hepatitis B virus (HBV) remains a global health challenge. Approximately 292 million people worldwide are chronically infected with HBV and the annual mortality from the infection is approaching 900,000. Despite the availability of an effective prophylactic vaccine, millions of individuals are [...] Read more.
Infection with hepatitis B virus (HBV) remains a global health challenge. Approximately 292 million people worldwide are chronically infected with HBV and the annual mortality from the infection is approaching 900,000. Despite the availability of an effective prophylactic vaccine, millions of individuals are at risk of potentially fatal complicating cirrhosis and hepatocellular carcinoma. Current drug treatments can suppress viral replication, slow the progression of liver fibrosis, and reduce infectivity, but can rarely clear the viral covalently closed circular DNA (cccDNA) that is responsible for HBV persistence. Alternative therapeutic strategies, including those based on viral gene silencing by harnessing the RNA interference (RNAi) pathway, effectively suppress HBV replication and thus hold promise. RNAi-based silencing of certain viral genes may even lead to disabling of cccDNA during chronic infection. This review summarizes different RNAi activators that have been tested against HBV, the advances with vectors used to deliver artificial potentially therapeutic RNAi sequences to the liver, and the current status of preclinical and clinical investigation. Full article
(This article belongs to the Special Issue RNA Interference (RNAi) for Antiviral Therapy)
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