Alina R Fernandes
Part II: Functional Delivery of a Neurotherapeutic Gene to Neural Stem Cells using Minicircle DNA and Nanoparticles: Translational advantages for Regenerative Neurology
Fernandes, Alina R; Chari, Divya M
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.
Citation
Fernandes, A. R., & Chari, D. M. (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, 300-310. https://doi.org/10.1016/j.jconrel.2016.06.039
Acceptance Date | Jun 27, 2016 |
---|---|
Publication Date | Jun 28, 2016 |
Journal | Journal of Controlled Release |
Print ISSN | 0168-3659 |
Publisher | Elsevier |
Pages | 300-310 |
DOI | https://doi.org/10.1016/j.jconrel.2016.06.039 |
Keywords | BDNF; minicircle; magnetofection; neural stem cells; genetic engineering |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S0168365916304163 |
Files
D Chari - Part II - Functional Delivery of a Neurotheraputic Gene to Neural Stem Cells using Minicircle DNA and Nanoparticles.pdf
(1.7 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by-nc-nd/4.0/
You might also like
In vitro model of neurotrauma using the chick embryo to test regenerative bioimplantation.
(2023)
Journal Article
Evaluating the Feasibility of Hydrogel-Based Neural Cell Sprays
(2023)
Journal Article
Systematic Alignment Analysis of Neural Transplant Cells in Electrospun Nanofibre Scaffolds
(2022)
Journal Article
EP-273 Magnetic nanoparticle administration to a model of penetrating neurotrauma in vitro
(2022)
Journal Article
Downloadable Citations
About Keele Repository
Administrator e-mail: research.openaccess@keele.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search