http://www.mdpi.com/journal/viruses/special_issues/viral-vector-systems/ Submission Information All papers should be submitted to viruses@mdpi.com. To be published continuously until the deadline and papers will be listed together at the special issue website. Submitted papers should not have been published nor be under consideration for publication elsewhere. All papers are refereed through a peer-review process. A guide for authors is available on the Instructions for Authors page. Viruses is a new international, peer-reviewed, quarterly open access journal published by MDPI. Article Processing Charges (APC) for publication in this Open Access journal are waived for well-prepared manuscripts submitted by 30 June 2010. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections. http://www.mdpi.com/1999-4915/2/4/1002/ Over the last three decades, interest in the field of gene therapy seems to have fluctuated between hot and cold. Encouraging pre-clinical and clinical data has demonstrated the potential of genetic therapies and yet setbacks in clinical trials have cast doubts in some minds over the clinical future of gene therapy [1-3]. In the last two years, a number of studies have demonstrated therapeutic benefits in clinical trials aimed towards specific monogenetic disorders [4-6], and this has brought renewed optimism to the field. [...] http://www.mdpi.com/1999-4915/2/4/1002/ Wed, 14 Apr 2010 00:00:00 CEST Viruses 2010-04-14 2 4 Editorial 1002 1007 1999-4915 Novel Viral Vector Systems for Gene Therapy 2010-04-14 doi: 10.3390/v2041002 Stone http://www.mdpi.com/1999-4915/2/2/468/ Covalent modification with polyethylene glycol (PEG), a non-toxic polymer used in food, cosmetic and pharmaceutical preparations for over 60 years, can profoundly influence the pharmacokinetic, pharmacologic and toxciologic profile of protein and peptide-based therapeutics. This review summarizes the history of PEGylation and PEG chemistry and highlights the value of this technology in the context of the design and development of recombinant viruses for gene transfer, vaccination and diagnostic purposes. Specific emphasis is placed on the application of this technology to the adenovirus, the most potent viral vector with the most highly characterized toxicity profile to date, in several animal models. http://www.mdpi.com/1999-4915/2/2/468/ Mon, 01 Feb 2010 00:00:00 CET Viruses 2010-02-01 2 2 Review 468 502 1999-4915 PEGylated Adenoviruses: From Mice to Monkeys 2010-02-01 doi: 10.3390/v2020468 Piyanuch Wonganan Maria A. Croyle http://www.mdpi.com/1999-4915/2/2/395/ Cystic fibrosis (CF) is a chronic autosomic recessive syndrome, caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, a chloride channel expressed on the apical side of the airway epithelial cells. The lack of CFTR activity brings a dysregulated exchange of ions and water through the airway epithelium, one of the main aspects of CF lung disease pathophysiology. Lentiviral (LV) vectors, of the Retroviridae family, show interesting properties for CF gene therapy, since they integrate into the host genome and allow long-lasting gene expression. Proof-of-principle that LV vectors can transduce the airway epithelium and correct the basic electrophysiological defect in CF mice has been given. Initial data also demonstrate that LV vectors can be repeatedly administered to the lung and do not give rise to a gross inflammatory process, although they can elicit a T cell-mediated response to the transgene. Future studies will clarify the efficacy and safety profile of LV vectors in new complex animal models with CF, such as ferrets and pigs. http://www.mdpi.com/1999-4915/2/2/395/ Fri, 29 Jan 2010 00:00:00 CET Viruses 2010-01-29 2 2 Review 395 412 1999-4915 Lentiviral Vectors and Cystic Fibrosis Gene Therapy 2010-01-29 doi: 10.3390/v2020395 Stefano Castellani Massimo Conese http://www.mdpi.com/1999-4915/2/2/334/ Cardiovascular disease represents the most common cause of mortality in the developed world but, despite two decades of promising pre-clinical research and numerous clinical trials, cardiovascular gene transfer has so far failed to demonstrate convincing benefits in the clinical setting. In this review we discuss the various targets which may be suitable for cardiovascular gene therapy and the viral vectors which have to date shown the most potential for clinical use. We conclude with a summary of the current state of clinical cardiovascular gene therapy and the key trials which are ongoing. http://www.mdpi.com/1999-4915/2/2/334/ Wed, 27 Jan 2010 00:00:00 CET Viruses 2010-01-27 2 2 Review 334 371 1999-4915 Development of Viral Vectors for Use in Cardiovascular Gene Therapy 2010-01-27 doi: 10.3390/v2020334 Paul D. Williams Parisa Ranjzad Salik J. Kakar Paul A. Kingston http://www.mdpi.com/1999-4915/2/1/244/ Numerous human genetic and acquired diseases could be corrected or ameliorated if viruses are harnessed to safely and effectively deliver therapeutic genes to diseased cells and tissues in vivo. Innate immune and inflammatory response represents one of the key stumbling blocks during the development of viral-based therapies. In this review, current data on the early innate immune responses to viruses and to the most commonly used gene therapy vectors (using adenovirus and adeno-associated virus) will be discussed. Recent findings in the field may help develop new approaches to moderate these innate immune anti-viral responses and thus improve the safety of viral vectors for human gene therapy applications. http://www.mdpi.com/1999-4915/2/1/244/ Tue, 19 Jan 2010 00:00:00 CET Viruses 2010-01-19 2 1 Review 244 261 1999-4915 Virus Infection Recognition and Early Innate Responses to Non-Enveloped Viral Vectors 2010-01-19 doi: 10.3390/v2010244 Dmitry M. Shayakhmetov http://www.mdpi.com/1999-4915/2/1/78/ Targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. In 2006, the world witnessed the first government-approved oncolytic virus for the treatment of head and neck cancer. It has been known for many years that viruses have the ability to replicate in and lyse cancer cells. Although encouraging results have been demonstrated in vitro and in animal models, most oncolytic viruses have failed to impress in the clinical setting. The explanation is multifactorial, determined by the complex interactions between the tumor and its microenvironment, the virus, and the host immune response. This review focuses on discussion of the obstacles that oncolytic virotherapy faces and recent advances made to overcome them, with particular reference to adenoviruses. http://www.mdpi.com/1999-4915/2/1/78/ Mon, 11 Jan 2010 00:00:00 CET Viruses 2010-01-11 2 1 Review 78 106 1999-4915 Oncolytic Viruses for Cancer Therapy: Overcoming the Obstacles 2010-01-11 doi: 10.3390/v2010078 Han Hsi Wong Nicholas R. Lemoine Yaohe Wang http://www.mdpi.com/1999-4915/2/1/1/ Technological advances and increasingly cost-effect methodologies in DNA sequencing and computational analysis are providing genome and proteome data for human adenovirus research. Applying these tools, data and derived knowledge to the development of vaccines against these pathogens will provide effective prophylactics. The same data and approaches can be applied to vector development for gene delivery in gene therapy and vaccine delivery protocols. Examination of several field strain genomes and their analyses provide examples of data that are available using these approaches. An example of the development of HAdV-B3 both as a vaccine and also as a vector is presented. http://www.mdpi.com/1999-4915/2/1/1/ Wed, 06 Jan 2010 00:00:00 CET Viruses 2010-01-06 2 1 Review 1 26 1999-4915 Applying Genomic and Bioinformatic Resources to Human Adenovirus Genomes for Use in Vaccine Development and for Applications in Vector Development for Gene Delivery 2010-01-06 doi: 10.3390/v2010001 Jason Seto Michael P. Walsh Padmanabhan Mahadevan Qiwei Zhang Donald Seto http://www.mdpi.com/1999-4915/1/3/1295/ The turbulent history of clinical trials in viral gene therapy has taught us important lessons about vector design and safety issues. Much effort was spent on analyzing genotoxicity after somatic integration of therapeutic DNA into the host genome. Based on these findings major improvements in vector design including the development of viral hybrid vectors for somatic integration have been achieved. This review provides a state-of-the-art overview of available hybrid vectors utilizing viruses for high transduction efficiencies in concert with various integration machineries for random and targeted integration patterns. It discusses advantages but also limitations of each vector system. http://www.mdpi.com/1999-4915/1/3/1295/ Tue, 15 Dec 2009 00:00:00 CET Viruses 2009-12-15 1 3 Review 1295 1324 1999-4915 Viral Hybrid Vectors for Somatic Integration - Are They the Better Solution? 2009-12-15 doi: 10.3390/v1031295 Nadine Müther Nadja Noske Anja Ehrhardt http://www.mdpi.com/1999-4915/1/3/594/ Since its emergence onto the gene therapy scene nearly 25 years ago, the replication-defective Herpes Simplex Virus Type-1 (HSV-1) amplicon has gained significance as a versatile gene transfer platform due to its extensive transgene capacity, widespread cellular tropism, minimal immunogenicity, and its amenability to genetic manipulation. Herein, we detail the recent advances made with respect to the design of the HSV amplicon, its numerous in vitro and in vivo applications, and the current impediments this virus-based gene transfer platform faces as it navigates a challenging path towards future clinical testing. http://www.mdpi.com/1999-4915/1/3/594/ Thu, 29 Oct 2009 00:00:00 CET Viruses 2009-10-29 1 3 Review 594 629 1999-4915 Herpes Virus Amplicon Vectors 2009-10-29 doi: 10.3390/v1030594 Suresh De Silva William J. Bowers http://www.mdpi.com/1999-4915/1/1/13/ Alphaviruses are enveloped single stranded RNA viruses, which as gene therapy vectors provide high-level transient gene expression. Semliki Forest virus (SFV), Sindbis virus (SIN) and Venezuelan Equine Encephalitis (VEE) virus have been engineered as efficient replication-deficient and -competent expression vectors. Alphavirus vectors have frequently been used as vehicles for tumor vaccine generation. Moreover, SFV and SIN vectors have been applied for intratumoral injections in animals implanted with tumor xenografts. SIN vectors have demonstrated natural tumor targeting, which might permit systemic vector administration. Another approach for systemic delivery of SFV has been to encapsulate replication-deficient viral particles in liposomes, which can provide passive targeting to tumors and allow repeated administration without host immune responses. This approach has demonstrated safe delivery of encapsulated SFV particles to melanoma and kidney carcinoma patients in a phase I trial. Finally, the prominent neurotropism of alphaviruses make them attractive for the treatment of CNS-related diseases. http://www.mdpi.com/1999-4915/1/1/13/ Tue, 21 Apr 2009 00:00:00 CEST Viruses 2009-04-21 1 1 Review 13 25 1999-4915 Alphaviruses in Gene Therapy 2009-04-21 doi: 10.3390/v1010013 Kenneth Lundstrom