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      Immune Activities of Polycationic Vectors for Gene Delivery

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          Abstract

          Polycationic vectors are used widely in the field of gene delivery, while currently their immune activities in vivo are poorly understood. In this comprehensive review, we aim to present an overview of existing mechanisms of adverse immune responses induced by the polycation/gene complexes, which includes the polycations themselves, the gene sequences and the ROS produced by them. These causes can induce pro-inflammatory cytokines, hypersensitivity as well as the activation of toll-like receptors, and finally the immunostimulation occur. In addition, we introduce some different opinions and research results on the immunogenicity of classical polycations such as polylysine (PLL), polyethyleneimine (PEI), polyamidoamine dendrimers (PAMAM), chitosan and gelatin, most of which have immunogenicity and can induce immunoreactions in vivo. The methods now used to adjust their immunogenicity are shown in the final part of this review. Nowadays, there is still no accurate conclusion on immunogenicity of polycations, which confuses researchers seriously in in vivo test. We conclude that further research is needed in order to skillfully utilize or inhibit the immunogenicity of these polycationic vectors.

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          Most cited references63

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          Progress and problems with the use of viral vectors for gene therapy.

          Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine. With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.
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            Starburst Dendrimers: Molecular-Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter

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              Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy.

              An important limitation that has emerged in the use of adenoviruses for gene therapy has been loss of recombinant gene expression that occurs concurrent with the development of pathology in the organ expressing the transgene. We have used liver-directed approaches to gene therapy in mice to study mechanisms that underlie the problems with transient expression and pathology that have characterized in vivo applications of first-generation recombinant adenoviruses (i.e., those deleted of E1a and E1b). Our data are consistent with the following hypothesis. Cells harboring the recombinant viral genome express the transgene as desired; however, low-level expression of viral genes also occurs. A virus-specific cellular immune response is stimulated that leads to destruction of the genetically modified hepatocytes, massive hepatitis, and repopulation of the liver with nontransgene-containing hepatocytes. These findings suggest approaches for improving recombinant adenoviruses that are based on further crippling the virus to limit expression of nondeleted viral genes.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                04 August 2017
                2017
                : 8
                : 510
                Affiliations
                [1] 1School of Pharmacy, Shanghai Jiao Tong University Shanghai, China
                [2] 2Department of Neurology, Jinshan Hospital, Fudan University Shanghai, China
                [3] 3Department of Cancer Biology, Dana-Farber Cancer Institute Boston, MA, United States
                [4] 4Shanghai Sixth People's Hospital East Campus, Shanghai University of Medicine and Health Shanghai, China
                Author notes

                Edited by: Claudio Bucolo, University of Catania, Italy

                Reviewed by: Blaine Pfeifer, University at Buffalo, United States; Sandor-Kerpel-Fronius, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Hungary

                *Correspondence: Yinghui Chen cyh1973131@ 123456163.com

                This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2017.00510
                5543280
                a59df92d-492c-4d1c-92d5-0c84e5a50083
                Copyright © 2017 Zhao, Li, Zhao, Cheng, Yang, Fang, Xie, Liu, Chen, Ouyang and Yuan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 May 2017
                : 20 July 2017
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 77, Pages: 8, Words: 6249
                Categories
                Pharmacology
                Mini Review

                Pharmacology & Pharmaceutical medicine
                polycationic vectors,gene delivery system,immune activities,mechanisms,immunoreactions

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