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Sci Rep. 2016 Jan 20;6:19579. doi: 10.1038/srep19579.

Noninvasive, Targeted, and Non-Viral Ultrasound-Mediated GDNF-Plasmid Delivery for Treatment of Parkinson's Disease.

Author information

1
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 30013 Taiwan.
2
Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Taoyuan, 33302 Taiwan.
3
Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013 Taiwan.
4
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529 Taiwan.
5
Department of Biomedical Engineering, National Yang Ming University, Taipei, 11221 Taiwan.
6
Department of Electrical Engineering, Chang-Gung University, Taoyuan, 33302 Taiwan.

Abstract

Glial cell line-derived neurotrophic factor (GDNF) supports the growth and survival of dopaminergic neurons. CNS gene delivery currently relies on invasive intracerebral injection to transit the blood-brain barrier. Non-viral gene delivery via systematic transvascular route is an attractive alternative because it is non-invasive, but a high-yield and targeted gene-expressed method is still lacking. In this study, we propose a novel non-viral gene delivery approach to achieve targeted gene transfection. Cationic microbubbles as gene carriers were developed to allow the stable formation of a bubble-GDNF gene complex, and transcranial focused ultrasound (FUS) exposure concurrently interacting with the bubble-gene complex allowed transient gene permeation and induced local GDNF expression. We demonstrate that the focused ultrasound-triggered GDNFp-loaded cationic microbubbles platform can achieve non-viral targeted gene delivery via a noninvasive administration route, outperform intracerebral injection in terms of targeted GDNF delivery of high-titer GDNF genes, and has a neuroprotection effect in Parkinson's disease (PD) animal models to successfully block PD syndrome progression and to restore behavioral function. This study explores the potential of using FUS and bubble-gene complexes to achieve noninvasive and targeted gene delivery for the treatment of neurodegenerative disease.

PMID:
26786201
PMCID:
PMC4726227
DOI:
10.1038/srep19579
[Indexed for MEDLINE]
Free PMC Article

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