http://www.mdpi.com/journal/viruses/special_issues/retroviral-vect/ {snippet name="submission_info"} http://www.mdpi.com/1999-4915/3/6/677/ 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. http://www.mdpi.com/1999-4915/3/6/677/ Fri, 03 Jun 2011 00:00:00 CEST Viruses 2011-06-03 3 6 Review 677 713 1999-4915 Gammaretroviral Vectors: Biology, Technology and Application 2011-06-03 doi: 10.3390/v3060677 Tobias Maetzig Melanie Galla Christopher Baum Axel Schambach http://www.mdpi.com/1999-4915/3/5/561/ 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. http://www.mdpi.com/1999-4915/3/5/561/ Wed, 11 May 2011 00:00:00 CEST Viruses 2011-05-11 3 5 Review 561 585 1999-4915 Foamy Virus Biology and Its Application for Vector Development 2011-05-11 doi: 10.3390/v3050561 Dirk Lindemann Axel Rethwilm http://www.mdpi.com/1999-4915/3/5/429/ 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. http://www.mdpi.com/1999-4915/3/5/429/ Fri, 29 Apr 2011 00:00:00 CEST Viruses 2011-04-29 3 5 Review 429 455 1999-4915 Retroviral Vectors: Post Entry Events and Genomic Alterations 2011-04-29 doi: 10.3390/v3050429 Ali Nowrouzi Hanno Glimm Christof Von Kalle Manfred Schmidt http://www.mdpi.com/1999-4915/3/2/132/ 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. http://www.mdpi.com/1999-4915/3/2/132/ Mon, 14 Feb 2011 00:00:00 CET Viruses 2011-02-14 3 2 Review 132 159 1999-4915 The Inside Out of Lentiviral Vectors 2011-02-14 doi: 10.3390/v3020132 Stéphanie Durand Andrea Cimarelli