Document Detail


Systemic gene transfer of polyethylenimine (PEI)-plasmid DNA complexes to neonatal mice.
MedLine Citation:
PMID:  21192993     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Non-viral vectors have not been extensively investigated in neonatal mice due to the poor efficiency of the delivery methods available. Understanding the effects of non-viral vectors during early development is vital to develop safe gene therapy treatments where irreversible pathological processes may be avoided by early gene reconstitution. Here we describe a simple and effective method for the systemic administration of non-viral vectors via the superior temporal vein of mouse pups at 1.5days of age. We show that injection of polyethylenimine (PEI)-complexed plasmid DNA (pDNA) intravenously results in effective transfection in the liver, lung, heart, spleen, brain and kidney. We also investigate the specific targeting of transgene expression to the proliferating neonate liver using a liver-specific plasmid containing a Scaffold Matrix Attachment Region (S/MAR) element, which has previously been shown to confer long-term expression in adult mouse liver. Using bioluminescent imaging, a gradual increase in transgene expression was observed which peaked at days 11-12, before the reduction of expression to background levels by day 25, suggestive of vector copy number loss. We conclude that non-viral vectors can successfully be used for systemic delivery to neonatal mice and that this technique is likely to open a host of early therapeutic possibilities for gene transfer by a range of non-viral vector formulations.
Authors:
Suet Ping Wong; Orestis Argyros; Steven J Howe; Richard P Harbottle
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-28
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  -     ISSN:  1873-4995     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010. Published by Elsevier B.V.
Affiliation:
Gene Therapy Research Group, Section of Molecular and Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
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