59
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Progresses towards safe and efficient gene therapy vectors

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The emergence of genetic engineering at the beginning of the 1970′s opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors.

          Related collections

          Most cited references237

          • Record: found
          • Abstract: found
          • Article: not found

          Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer.

          We report the death of an 18-year-old male with partial ornithine transcarbamylase (OTC) deficiency who participated in a pilot (safety) study of gene therapy. The vector used for this trial was based on human adenovirus type 5, deleted in E1 and E4, and contained human OTC cDNA. It was infused into the right hepatic artery at a dose of 6x10(11)particles/kg. Approximately 18 h. following gene transfer the subject was noted to have altered mental status and jaundice--clinical signs not seen in any of the first 17 subjects in this study. Subsequently, his clinical course was marked by systemic inflammatory response syndrome, biochemically detectable disseminated intravascular coagulation, and multiple organ system failure, leading to death 98 h following gene transfer. Post-mortem examination was consistent with the clinical course, and vector DNA sequences were readily detectable in most tissues. The subject had high serum levels of IL-6 and IL-10 but normal TNFalpha immediately after infusion of the vector. This experience points to the limitations of animal studies in predicting human responses, the steep toxicity curve for replication defective adenovirus vectors, substantial subject-to-subject variation in host responses to systemically administered vectors, and the need for further study of the immune response to these vectors.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas.

            We have created a double mutant of the herpes simplex virus (HSV) type 1 (termed G207) with favourable properties for treating human malignant brain tumours: replication-competence in glioblastoma cells (and other dividing cells), attenuated neurovirulence, temperature sensitivity, ganciclovir hypersensitivity, and the presence of an easily detectable histochemical marker. G207 has deletions at both gamma 34.5 (RL1) loci and a lacZ gene insertion inactivating the ICP6 gene (UL39). G207 kills human glioma cells in monolayer cultures. In nude mice harbouring subcutaneous or intracerebral U-87MG gliomas, intraneoplastic inoculation with G207 causes decreased tumour growth and/or prolonged survival. G207 is avirulent upon intracerebral inoculation of mice and HSV-sensitive non-human primates. These results suggest that G207 should be considered for clinical evaluation in the treatment of glioblastomas.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Endgame: glybera finally recommended for approval as the first gene therapy drug in the European union.

                Bookmark

                Author and article information

                Journal
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                13 October 2015
                4 September 2015
                : 6
                : 31
                : 30675-30703
                Affiliations
                1 Research Center for Functional Genomics, Biomedicine and Translational Medicine, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj Napoca, Romania
                2 Department of Immunology and Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
                3 Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
                4 Department of Molecular Biology and Genetics, Canik Başari University, Samsun, Turkey
                5 Department of Immunology, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj Napoca, Romania
                6 Department of Functional Genomics and Experimental Pathology, Oncological Institute “Prof. Dr. Ion Chiricuţă”, Cluj Napoca, Romania
                7 BlueBird Bio, MA, USA
                8 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
                9 Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
                10 Department of Physiopathology, Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, Cluj Napoca, Romania
                Author notes
                Correspondence to: George A. Calin, gcalin@ 123456mdanderson.org
                Article
                10.18632/oncotarget.5169
                4741561
                26362400
                f92e75cd-33f6-403b-b6f5-5ede28f92866
                Copyright: © 2015 Chira et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 June 2015
                : 22 August 2015
                Categories
                Review

                Oncology & Radiotherapy
                gene therapy,non-viral vectors,viral vectors,hybrid vectors,aavp
                Oncology & Radiotherapy
                gene therapy, non-viral vectors, viral vectors, hybrid vectors, aavp

                Comments

                Comment on this article