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Mol Ther. 2009 Apr;17(4):641-50. doi: 10.1038/mt.2009.2. Epub 2009 Feb 17.

Long-term transgene expression in the central nervous system using DNA nanoparticles.

Author information

1
Department of Neurosurgery, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0305, USA. David.Yurek@uky.edu

Abstract

This study demonstrates proof of concept for delivery and expression of compacted plasmid DNA in the central nervous system. Plasmid DNA was compacted with polyethylene glycol substituted lysine 30-mer peptides, forming rod-like nanoparticles with diameters between 8 and 11 nm. Here we show that an intracerebral injection of compacted DNA can transfect both neurons and glia, and can produce transgene expression in the striatum for up to 8 weeks, which was at least 100-fold greater than intracerebral injections of naked DNA plasmids. Bioluminescent imaging (BLI) of injected animals at the 11th postinjection week revealed significantly higher transgene activity in animals receiving compacted DNA plasmids when compared to animals receiving naked DNA. There was minimal evidence of brain inflammation. Intrastriatal injections of a compacted plasmid encoding for glial cell line-derived neurotrophic factor (pGDNF) resulted in a significant overexpression of GDNF protein in the striatum 1-3 weeks after injection.

PMID:
19223866
PMCID:
PMC2835115
DOI:
10.1038/mt.2009.2
[Indexed for MEDLINE]
Free PMC Article

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