A preliminary study of Parkinson's gene therapy via sono-magnetic sensing gene vector for conquering extra/intracellular barriers in mice

Chun Yao Wu, Rih Yang Huang, En Chi Liao, Yu Chun Lin, Yi Ju Ho, Chien Wen Chang, Hong Lin Chan, Ying Zu Huang, Tsung Hsun Hsieh, Ching Hsiang Fan, Chih Kuang Yeh

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)786-799
頁數14
期刊Brain Stimulation
13
發行號3
DOIs
出版狀態Published - 2020 五月 1

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Neuroscience(all)
  • Clinical Neurology

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