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Chitosan in Non-Viral Gene Delivery: Role of Structure, Characterization Methods, and Insights in Cancer and Rare Diseases Therapies

ChiPro GmbH, Anne-Conway-Street 1, 28359 Bremen, Germany
Lung Biology Group, Department Clinical Microbiology, RCSI, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK
Author to whom correspondence should be addressed.
Polymers 2018, 10(4), 444;
Received: 9 March 2018 / Revised: 4 April 2018 / Accepted: 11 April 2018 / Published: 15 April 2018
(This article belongs to the Special Issue Advances in Chitin/Chitosan Characterization and Applications)
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Non-viral gene delivery vectors have lagged far behind viral ones in the current pipeline of clinical trials of gene therapy nanomedicines. Even when non-viral nanovectors pose less safety risks than do viruses, their efficacy is much lower. Since the early studies to deliver pDNA, chitosan has been regarded as a highly attractive biopolymer to deliver nucleic acids intracellularly and induce a transgenic response resulting in either upregulation of protein expression (for pDNA, mRNA) or its downregulation (for siRNA or microRNA). This is explained as the consequence of a multi-step process involving condensation of nucleic acids, protection against degradation, stabilization in physiological conditions, cellular internalization, release from the endolysosome (“proton sponge” effect), unpacking and enabling the trafficking of pDNA to the nucleus or the siRNA to the RNA interference silencing complex (RISC). Given the multiple steps and complexity involved in the gene transfection process, there is a dearth of understanding of the role of chitosan’s structural features (Mw and degree of acetylation, DA%) on each step that dictates the net transfection efficiency and its kinetics. The use of fully characterized chitosan samples along with the utilization of complementary biophysical and biological techniques is key to bridging this gap of knowledge and identifying the optimal chitosans for delivering a specific gene. Other aspects such as cell type and administration route are also at play. At the same time, the role of chitosan structural features on the morphology, size and surface composition of synthetic virus-like particles has barely been addressed. The ongoing revolution brought about by the recent discovery of CRISPR-Cas9 technology will undoubtedly be a game changer in this field in the short term. In the field of rare diseases, gene therapy is perhaps where the greatest potential lies and we anticipate that chitosans will be key players in the translation of research to the clinic. View Full-Text
Keywords: gene delivery; non-viral vectors; chitosan structure; pDNA; siRNA gene delivery; non-viral vectors; chitosan structure; pDNA; siRNA

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Santos-Carballal, B.; Fernández Fernández, E.; Goycoolea, F.M. Chitosan in Non-Viral Gene Delivery: Role of Structure, Characterization Methods, and Insights in Cancer and Rare Diseases Therapies. Polymers 2018, 10, 444.

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