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Special Issue "Retroviral Vectors"

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 July 2014)

Special Issue Editors

Guest Editor
Prof. Dr. Dirk Lindemann

Institute of Virology, Technische Universität Dresden
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Former Guest Editor
Prof. Dr. Axel Rethwilm

Institut für Virologie und Immunbiologie, Universität Würzburg, Versbacher Straße 7, 97078 Würzburg, Germany
Prof. Axel Rethwilm sadly passed away on July 29th 2014. We offer our condolences to his family and consider it a privilege to have had the opportunity to work with him. The university has published this announcement in his honor:[http://www.uni-wuerzburg.de/sonstiges/meldungen/single/artikel/verdienste/]
Running of the Special Issue has been kindly continued by: Prof. Dr. Dirk Lindemann

Special Issue Information

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 1500 CHF (Swiss Francs).

Published Papers (7 papers)

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Review

Open AccessReview Alpharetroviral Vectors: From a Cancer-Causing Agent to a Useful Tool for Human Gene Therapy
Viruses 2014, 6(12), 4811-4838; doi:10.3390/v6124811
Received: 26 September 2014 / Revised: 7 November 2014 / Accepted: 20 November 2014 / Published: 5 December 2014
Cited by 5 | PDF Full-text (786 KB) | HTML Full-text | XML Full-text
Abstract
Gene therapy using integrating retroviral vectors has proven its effectiveness in several clinical trials for the treatment of inherited diseases and cancer. However, vector-mediated adverse events related to insertional mutagenesis were also observed, emphasizing the need for safer therapeutic vectors. Paradoxically, alpharetroviruses, originally
[...] Read more.
Gene therapy using integrating retroviral vectors has proven its effectiveness in several clinical trials for the treatment of inherited diseases and cancer. However, vector-mediated adverse events related to insertional mutagenesis were also observed, emphasizing the need for safer therapeutic vectors. Paradoxically, alpharetroviruses, originally discovered as cancer-causing agents, have a more random and potentially safer integration pattern compared to gammaretro- and lentiviruses. In this review, we provide a short overview of the history of alpharetroviruses and explain how they can be converted into state-of-the-art gene delivery tools with improved safety features. We discuss development of alpharetroviral vectors in compliance with regulatory requirements for clinical translation, and provide an outlook on possible future gene therapy applications. Taken together, this review is a broad overview of alpharetroviral vectors spanning the bridge from their parental virus discovery to their potential applicability in clinical settings. Full article
(This article belongs to the Special Issue Retroviral Vectors)
Open AccessReview Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy
Viruses 2014, 6(11), 4140-4164; doi:10.3390/v6114140
Received: 4 August 2014 / Revised: 9 October 2014 / Accepted: 21 October 2014 / Published: 31 October 2014
Cited by 6 | PDF Full-text (1056 KB) | HTML Full-text | XML Full-text
Abstract
Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth
[...] Read more.
Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth of a transformed clonal population. This clonal expansion is influenced by the integration site profile of the viral integrase, the transgene expressed, and the effect of the viral promoters on the neighbouring host genome. Infection with the pathogenic human retrovirus HTLV-1 also causes clonal expansion of cells containing an integrated HTLV-1 provirus. Although the majority of HTLV-1-infected people remain asymptomatic, up to 5% develop an aggressive T cell malignancy. In this review we discuss recent findings on the role of the genomic integration site in determining the clonality and the potential for malignant transformation of cells carrying integrated HTLV-1 or gene therapy vectors, and how these results have contributed to the understanding of HTLV-1 pathogenesis and to improvements in gene therapy vector safety. Full article
(This article belongs to the Special Issue Retroviral Vectors)
Open AccessReview Retroviral Vectors for Analysis of Viral Mutagenesis and Recombination
Viruses 2014, 6(9), 3612-3642; doi:10.3390/v6093612
Received: 15 August 2014 / Revised: 15 September 2014 / Accepted: 17 September 2014 / Published: 24 September 2014
PDF Full-text (793 KB) | HTML Full-text | XML Full-text
Abstract
Retrovirus population diversity within infected hosts is commonly high due in part to elevated rates of replication, mutation, and recombination. This high genetic diversity often complicates the development of effective diagnostics, vaccines, and antiviral drugs. This review highlights the diverse vectors and approaches
[...] Read more.
Retrovirus population diversity within infected hosts is commonly high due in part to elevated rates of replication, mutation, and recombination. This high genetic diversity often complicates the development of effective diagnostics, vaccines, and antiviral drugs. This review highlights the diverse vectors and approaches that have been used to examine mutation and recombination in retroviruses. Retroviral vectors for these purposes can broadly be divided into two categories: those that utilize reporter genes as mutation or recombination targets and those that utilize viral genes as targets of mutation or recombination. Reporter gene vectors greatly facilitate the detection, quantification, and characterization of mutants and/or recombinants, but may not fully recapitulate the patterns of mutagenesis or recombination observed in native viral gene sequences. In contrast, the detection of mutations or recombination events directly in viral genes is more biologically relevant but also typically more challenging and inefficient. We will highlight the advantages and disadvantages of the various vectors and approaches used as well as propose ways in which they could be improved. Full article
(This article belongs to the Special Issue Retroviral Vectors)
Open AccessReview Gammaretroviral Vectors: Biology, Technology and Application
Viruses 2011, 3(6), 677-713; doi:10.3390/v3060677
Received: 8 March 2011 / Revised: 3 May 2011 / Accepted: 9 May 2011 / Published: 3 June 2011
Cited by 31 | PDF Full-text (835 KB)
Abstract
Retroviruses are evolutionary optimized gene carriers that have naturally adapted to their hosts to efficiently deliver their nucleic acids into the target cell chromatin, thereby overcoming natural cellular barriers. Here we will review—starting with a deeper look into retroviral biology—how Murine Leukemia Virus
[...] Read more.
Retroviruses are evolutionary optimized gene carriers that have naturally adapted to their hosts to efficiently deliver their nucleic acids into the target cell chromatin, thereby overcoming natural cellular barriers. Here we will review—starting with a deeper look into retroviral biology—how Murine Leukemia Virus (MLV), a simple gammaretrovirus, can be converted into an efficient vehicle of genetic therapeutics. Furthermore, we will describe how more rational vector backbones can be designed and how these so-called self-inactivating vectors can be pseudotyped and produced. Finally, we will provide an overview on existing clinical trials and how biosafety can be improved. Full article
(This article belongs to the Special Issue Retroviral Vectors)
Open AccessReview Foamy Virus Biology and Its Application for Vector Development
Viruses 2011, 3(5), 561-585; doi:10.3390/v3050561
Received: 7 March 2011 / Revised: 21 April 2011 / Accepted: 23 April 2011 / Published: 11 May 2011
Cited by 45 | PDF Full-text (750 KB) | HTML Full-text | XML Full-text
Abstract
Spuma- or foamy viruses (FV), endemic in most non-human primates, cats, cattle and horses, comprise a special type of retrovirus that has developed a replication strategy combining features of both retroviruses and hepadnaviruses. Unique features of FVs include an apparent apathogenicity in natural
[...] Read more.
Spuma- or foamy viruses (FV), endemic in most non-human primates, cats, cattle and horses, comprise a special type of retrovirus that has developed a replication strategy combining features of both retroviruses and hepadnaviruses. Unique features of FVs include an apparent apathogenicity in natural hosts as well as zoonotically infected humans, a reverse transcription of the packaged viral RNA genome late during viral replication resulting in an infectious DNA genome in released FV particles and a special particle release strategy depending capsid and glycoprotein coexpression and specific interaction between both components. In addition, particular features with respect to the integration profile into the host genomic DNA discriminate FV from orthoretroviruses. It appears that some inherent properties of FV vectors set them favorably apart from orthoretroviral vectors and ask for additional basic research on the viruses as well as on the application in Gene Therapy. This review will summarize the current knowledge of FV biology and the development as a gene transfer system. Full article
(This article belongs to the Special Issue Retroviral Vectors)
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Figure 1

Open AccessReview Retroviral Vectors: Post Entry Events and Genomic Alterations
Viruses 2011, 3(5), 429-455; doi:10.3390/v3050429
Received: 9 February 2011 / Revised: 24 March 2011 / Accepted: 5 April 2011 / Published: 29 April 2011
Cited by 14 | PDF Full-text (687 KB)
Abstract
The curative potential of retroviral vectors for somatic gene therapy has been demonstrated impressively in several clinical trials leading to sustained long-term correction of the underlying genetic defect. Preclinical studies and clinical monitoring of gene modified hematopoietic stem and progenitor cells in patients
[...] Read more.
The curative potential of retroviral vectors for somatic gene therapy has been demonstrated impressively in several clinical trials leading to sustained long-term correction of the underlying genetic defect. Preclinical studies and clinical monitoring of gene modified hematopoietic stem and progenitor cells in patients have shown that biologically relevant vector induced side effects, ranging from in vitro immortalization to clonal dominance and oncogenesis in vivo, accompany therapeutic efficiency of integrating retroviral gene transfer systems. Most importantly, it has been demonstrated that the genotoxic potential is not identical among all retroviral vector systems designed for clinical application. Large scale viral integration site determination has uncovered significant differences in the target site selection of retrovirus subfamilies influencing the propensity for inducing genetic alterations in the host genome. In this review we will summarize recent insights gained on the mechanisms of insertional mutagenesis based on intrinsic target site selection of different retrovirus families. We will also discuss examples of side effects occurring in ongoing human gene therapy trials and future prospectives in the field. Full article
(This article belongs to the Special Issue Retroviral Vectors)
Open AccessReview The Inside Out of Lentiviral Vectors
Viruses 2011, 3(2), 132-159; doi:10.3390/v3020132
Received: 26 November 2010 / Revised: 25 January 2011 / Accepted: 8 February 2011 / Published: 14 February 2011
Cited by 17 | PDF Full-text (347 KB)
Abstract
Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we
[...] Read more.
Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them. Full article
(This article belongs to the Special Issue Retroviral Vectors)

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