A preliminary study of Parkinson’s gene therapy via sono-magnetic sensing gene vector for conquering extra/intracellular barriers in mice
| Autor: | Hong-Lin Chan, Yu-Chun Lin, Chun Yao Wu, Chien-Wen Chang, Ching Hsiang Fan, Yi Ju Ho, Rih Yang Huang, Chih-Kuang Yeh, En Chi Liao, Ying-Zu Huang, Tsung Hsun Hsieh |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Intracellular Fluid
Cell Survival Genetic enhancement Genetic Vectors Biophysics Mice Transgenic Gene delivery 050105 experimental psychology lcsh:RC321-571 Cell membrane 03 medical and health sciences Mice 0302 clinical medicine Neurotrophic factors Lysosome Cell Line Tumor Ultrasound medicine Animals Humans 0501 psychology and cognitive sciences Gene lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Blood-brain barrier Chemistry General Neuroscience Dopaminergic Neurons 05 social sciences Gene Transfer Techniques Extracellular Fluid Parkinson Disease Transfection Genetic Therapy Cell biology Mice Inbred C57BL medicine.anatomical_structure Magnetic Fields Parkinson’s disease Superparamagnetic iron oxide Neurology (clinical) 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Brain Stimulation, Vol 13, Iss 3, Pp 786-799 (2020) |
| Popis: | Background Non-virus genetic treatment for Parkinson’s disease (PD) via plasmid glial cell-line derived neurotrophic factor (pGDNF) has shown potential for repairing damaged dopaminergic neurons. However, development of this gene therapy is largely hampered by the insufficient transfection efficiency as a result of the cell membrane, lysosome, and cytoskeleton meshwork. Methods In this study, we propose the use of polyethylenimine (PEI)-superparamagnetic iron oxide-plasmid DNA (pDNA)-loaded microbubbles (PSp-MBs) in conjunction with focused ultrasound (FUS) and two-step magnetic navigation to provide cavitation, proton sponge effect and magnetic effects to increase the efficiency of gene delivery. Results The gene transfection rate in the proposed system was 2.2-fold higher than that of the commercial agent (TransIT®-LT1). The transfection rate could be boosted ∼11%, ∼10%, and 6% by cavitation-magnetic hybrid enhanced cell membrane permeabilization, proton sponge effect, and magnetic-assisted cytoskeleton-reorganization, respectively. In vivo data suggested that effective gene delivery with this system results in a 3.2-fold increase in recovery of dopaminergic neurons and a 3.9-fold improvement in the motor behavior when compared to untreated genetic PD mice. Conclusions We proposed that this novel FUS-magnetic hybrid gene delivery platform could be integrated with a variety of therapeutic genes for treating neurodegenerative diseases in the future. |
| Databáze: | OpenAIRE |
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