A preliminary study of Parkinson's gene therapy via sono-magnetic sensing gene vector for conquering extra/intracellular barriers in mice.
Brain Stimul
; 13(3): 786-799, 2020.
Article
in En
| MEDLINE
| ID: mdl-32289709
ABSTRACT
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 â¼11%, â¼10%, 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parkinson Disease
/
Genetic Therapy
/
Extracellular Fluid
/
Magnetic Fields
/
Genetic Vectors
/
Intracellular Fluid
Limits:
Animals
/
Humans
Language:
En
Journal:
Brain Stimul
Journal subject:
CEREBRO
Year:
2020
Document type:
Article
Affiliation country:
Taiwan