Fernandes, AR and Chari, DM (2016) Part II: Functional Delivery of a Neurotherapeutic Gene to Neural Stem Cells using Minicircle DNA and Nanoparticles: Translational advantages for Regenerative Neurology. Journal of Controlled Release. ISSN 0168-3659

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D Chari - Part II - Functional Delivery of a Neurotheraputic Gene to Neural Stem Cells using Minicircle DNA and Nanoparticles.pdf - Accepted Version
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Abstract

Both neurotrophin-based therapy and neural stem cell (NSC)-based strategies have progressed to clinical trials for treatment of neurological diseases and injuries. Brain-derived neurotrophic factor (BDNF) in particular can confer neuroprotective and neuro-regenerative effects in preclinical studies, complementing the cell replacement benefits of NSCs. Therefore, combining both approaches by genetically-engineering NSCs to express BDNF is an attractive approach to achieve combinatorial therapy for complex neural injuries. Current genetic engineering approaches almost exclusively employ viral vectors for gene delivery to NSCs though safety and scalability pose major concerns for clinical translation and applicability. Magnetofection, a non-viral gene transfer approach deploying magnetic nanoparticles and DNA with magnetic fields offers a safe alternative but significant improvements are required to enhance its clinical application for delivery of large sized therapeutic plasmids. Here, we demonstrate for the first time the feasibility of using minicircles with magnetofection technology to safely engineer NSCs to overexpress BDNF. Primary mouse NSCs overexpressing BDNF generated increased daughter neuronal cell numbers post-differentiation, with accelerated maturation over a four-week period. Based on our findings we highlight the clinical potential of minicircle/magnetofection technology for therapeutic delivery of key neurotrophic agents.

Item Type: Article
Uncontrolled Keywords: BDNF; minicircle; magnetofection; neural stem cells; genetic engineering
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 29 Jun 2016 08:30
Last Modified: 28 Jun 2017 01:30
URI: http://eprints.keele.ac.uk/id/eprint/1958

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