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      Recent advances in the development of gene delivery systems

      review-article
      1 , 2 , 3 , 4 , , 1 , 2
      Biomaterials Research
      BioMed Central
      Gene delivery system, Viral vectors, Non-viral vectors, RNA, DNA

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          Abstract

          Background

          Gene delivery systems are essentially necessary for the gene therapy of human genetic diseases. Gene therapy is the unique way that is able to use the adjustable gene to cure any disease. The gene therapy is one of promising therapies for a number of diseases such as inherited disorders, viral infection and cancers. The useful results of gene delivery systems depend open the adjustable targeting gene delivery systems. Some of successful gene delivery systems have recently reported for the practical application of gene therapy.

          Main body

          The recent developments of viral gene delivery systems and non-viral gene delivery systems for gene therapy have briefly reviewed. The viral gene delivery systems have discussed for the viral vectors based on DNA, RNA and oncolytic viral vectors. The non-viral gene delivery systems have also treated for the physicochemical approaches such as physical methods and chemical methods. Several kinds of successful gene delivery systems have briefly discussed on the bases of the gene delivery systems such as cationic polymers, poly(L-lysine), polysaccharides, and poly(ethylenimine)s.

          Conclusion

          The goal of the research for gene delivery system is to develop the clinically relevant vectors such as viral and non-viral vectors that use to combat elusive diseases such as AIDS, cancer, Alzheimer, etc. Next step research will focus on advancing DNA and RNA molecular technologies to become the standard treatment options in the clinical area of biomedical application.

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          Most cited references92

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          Polysaccharides-based nanoparticles as drug delivery systems.

          Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drug delivery systems. In particular, polysaccharides seem to be the most promising materials in the preparation of nanometeric carriers. This review relates to the newest developments in the preparation of polysaccharides-based nanoparticles. In this review, four mechanisms are introduced to prepare polysaccharides-based nanoparticles, that is, covalent crosslinking, ionic crosslinking, polyelectrolyte complex, and the self-assembly of hydrophobically modified polysaccharides.
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            Gene therapy clinical trials worldwide to 2017: An update

            To date, almost 2600 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our November 2017 update, we have entries on 2597 trials undertaken in 38 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and the genes that have been transferred. Details of the analyses presented, and our searchable database are available via The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in gene therapy clinical trials around the world, and discuss key trends since the previous review, namely the use of chimeric antigen receptor T cells for the treatment of cancer and advancements in genome editing technologies, which have the potential to transform the field moving forward.
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              The possible "proton sponge " effect of polyethylenimine (PEI) does not include change in lysosomal pH.

              Polycations such as polyethylenimine (PEI) are used in many novel nonviral vector designs and there are continuous efforts to increase our mechanistic understanding of their interactions with cells. Even so, the mechanism of polyplex escape from the endosomal/lysosomal pathway after internalization is still elusive. The "proton sponge " hypothesis remains the most generally accepted mechanism, although it is heavily debated. This hypothesis is associated with the large buffering capacity of PEI and other polycations, which has been interpreted to cause an increase in lysosomal pH even though no conclusive proof has been provided. In the present study, we have used a nanoparticle pH sensor that was developed for pH measurements in the endosomal/lysosomal pathway. We have carried out quantitative measurements of lysosomal pH as a function of PEI content and correlate the results to the "proton sponge " hypothesis. Our measurements show that PEI does not induce change in lysosomal pH as previously suggested and quantification of PEI concentrations in lysosomes makes it uncertain that the "proton sponge " effect is the dominant mechanism of polyplex escape.
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                Author and article information

                Contributors
                yongk.sung@utah.edu
                SW.Kim@pharm.utah.edu
                Journal
                Biomater Res
                Biomater Res
                Biomaterials Research
                BioMed Central (London )
                1226-4601
                2055-7124
                12 March 2019
                12 March 2019
                2019
                : 23
                : 8
                Affiliations
                [1 ]ISNI 0000 0001 2193 0096, GRID grid.223827.e, Department of Pharmaceutics and Pharmaceutical Chemistry, , University of Utah, ; Salt Lake City, UT 84112 USA
                [2 ]ISNI 0000 0001 2193 0096, GRID grid.223827.e, Center for Controlled Chemical Delivery, , University of Utah, ; Salt Lake City, UT 84112 USA
                [3 ]ISNI 0000 0001 0671 5021, GRID grid.255168.d, Department of Chemistry, , Dongguk University, ; Chung-gu, Seoul 04620 Korea
                [4 ]ISNI 0000 0001 2193 0096, GRID grid.223827.e, Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, , University of Utah, ; BPRB, Room 205, Salt Lake City, UT 84112 USA
                Author information
                http://orcid.org/0000-0001-7009-8822
                Article
                156
                10.1186/s40824-019-0156-z
                6417261
                30915230
                c5e2f74b-ffbe-4473-80cb-1922d3110a84
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 December 2018
                : 20 February 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000009, Foundation for the National Institutes of Health;
                Award ID: CA177932
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: CA177932
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                gene delivery system,viral vectors,non-viral vectors,rna,dna

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