Document Detail


CNS gene transfer mediated by a novel controlled release system based on DNA complexes of degradable polycation PPE-EA: a comparison with polyethylenimine/DNA complexes.
MedLine Citation:
PMID:  14681704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nonviral gene delivery systems based upon polycation/plasmid DNA complexes are quickly gaining recognition as an alternative to viral gene vectors for their potential in avoiding immunogenicity and toxicity problems inherent in viral systems. We investigated in this study the feasibility of using a controlled release system based on DNA complexed with a recently developed polymeric gene carrier, polyaminoethyl propylene phosphate (PPE-EA), to achieve gene transfer in the brain. A unique feature of this gene delivery system is the biodegradability of PPE-EA, which can provide a sustained release of DNA at different rates depending on the charge ratio of the polymer to DNA. PPE-EA/DNA complexes, naked DNA, and DNA complexed with polyethylenimine (PEI), a nondegradable cationic polymer known to be an effective gene carrier, were injected intracisternally into the mouse cerebrospinal fluid. Transgene expression mediated by naked DNA was mainly detected in the brain stem, a region close to the injection site. With either PPE-EA or PEI as a carrier, higher levels of gene expression could be detected in the cerebral cortex, basal ganglia, and diencephalons. Transgene expression in the brain mediated by PPE-EA/DNA complexes at an N/P ratio of 2 persisted for at least 4 weeks, with a significant higher level than that produced by either naked plasmid DNA or PEI/DNA at the 4-week time point. Furthermore, PPE-EA displayed much lower toxicity in cultured neural cells as compared to PEI and did not cause detectable pathological changes in the central nervous system (CNS). The results established the potential of PPE-EA as a new and biocompatible gene carrier to achieve sustained gene expression in the CNS.
Authors:
Y Li; J Wang; C G L Lee; C Y Wang; S J Gao; G P Tang; Y X Ma; H Yu; H-Q Mao; K W Leong; S Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gene therapy     Volume:  11     ISSN:  0969-7128     ISO Abbreviation:  Gene Ther.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2003-12-18     Completed Date:  2004-04-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  109-14     Citation Subset:  IM    
Affiliation:
Institute of Bioengineering and Nanotechnology, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / enzymology*
DNA / administration & dosage*
Gene Expression
Gene Therapy / methods*
Genetic Vectors / administration & dosage*,  genetics
Immunohistochemistry
Luciferases / genetics
Mice
Organophosphorus Compounds
Particle Size
Polyethyleneimine
Polymers
Transfection / methods
Chemical
Reg. No./Substance:
0/Organophosphorus Compounds; 0/Polymers; 0/poly(2-aminoethyl propylene phosphate); 9002-98-6/Polyethyleneimine; 9007-49-2/DNA; EC 1.13.12.-/Luciferases

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