Intracerebral injections of DNA nanoparticles encoding for a therapeutic gene provide partial neuroprotection in an animal model of neurodegeneration
| Autor: | Mark E. Cooper, Ulla Hasselrot, Linas Padegimas, David M. Yurek, Ozge Sesenoglu-Laird |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cell Survival Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering Substantia nigra Striatum Pharmacology Neuroprotection Rats Sprague-Dawley 03 medical and health sciences Neurotrophic factors Dopamine Glial cell line-derived neurotrophic factor medicine Animals Humans Neurotoxin General Materials Science Glial Cell Line-Derived Neurotrophic Factor biology Dopaminergic Neurons Neurodegeneration Gene Transfer Techniques DNA Genetic Therapy medicine.disease Molecular biology Disease Models Animal 030104 developmental biology nervous system biology.protein Nanoparticles Molecular Medicine medicine.drug |
| Zdroj: | Nanomedicine: Nanotechnology, Biology and Medicine. 13:2209-2217 |
| ISSN: | 1549-9634 |
| DOI: | 10.1016/j.nano.2017.06.010 |
| Popis: | This study reports proof of concept for administering compacted DNA nanoparticles (DNPs) intracerebrally as a means to protect against neurotoxin-induced neurodegeneration of dopamine (DA) neurons. In this study we used DNPs that encoded for human glial cell line-derived neurotrophic factor (hGDNF); GDNF is a potent neurotrophic factor for DA neurons. Intracerebral injections of DNPs into the striatum and/or substantia nigra were performed 1 week before treatment with a neurotoxin. We observed that the number of surviving DA cells, the density of DA fiber terminals and recovery of motor function were greater in animals injected with GDNF-encoding DNPs than in control animals receiving DNPs encoding for an inert reporter gene. The results of these studies are one of the first to demonstrate that a non-viral, synthetic nanoparticle can be used to deliver therapeutic genes to cells in the brain as a means to protect cells against neurotoxin-induced neurodegeneration. |
| Databáze: | OpenAIRE |
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