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

Brain Stimulation

Yi-Ju Ho¹  Chih-Kuang Yeh²  Rih-Yang Huang³  Hong-Lin Chan³  Chien-Wen Chang³  Chun-Yao Wu³  Ying-Zu Huang⁴  En-Chi Liao⁴  Yu-Chun Lin⁵  Tsung-Hsun Hsieh⁶  Ching-Hsiang Fan⁷ 

[1] Department of Molecular Science, National Tsing Hua University, Hsinchu, Taiwan;Neuroscience Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taipei, Taiwan;Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan;Department of Medical Science, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan;Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan;Neuroscience Research Center, Healthy Aging Research Center and Department of Neurology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taipei, Taiwan;;School of Physical Therapy &

关键词: Parkinson’s disease;    Gene delivery;    Ultrasound;    Blood-brain barrier;    Superparamagnetic iron oxide;   

DOI  :  

来源: DOAJ

【 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.

【 授权许可】

Unknown