Please use this identifier to cite or link to this item: https://doi.org/10.1038/sj.gt.3301794
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dc.titleEnhanced gene expression in mouse muscle by sustained release of plasmid DNA using PPE-EA as a carrier
dc.contributor.authorWang, J.
dc.contributor.authorZhang, P.-C.
dc.contributor.authorMao, H.-Q.
dc.contributor.authorLeong, K.W.
dc.date.accessioned2014-10-29T08:38:28Z
dc.date.available2014-10-29T08:38:28Z
dc.date.issued2002-09
dc.identifier.citationWang, J., Zhang, P.-C., Mao, H.-Q., Leong, K.W. (2002-09). Enhanced gene expression in mouse muscle by sustained release of plasmid DNA using PPE-EA as a carrier. Gene Therapy 9 (18) : 1254-1261. ScholarBank@NUS Repository. https://doi.org/10.1038/sj.gt.3301794
dc.identifier.issn09697128
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/107028
dc.description.abstractDelivery of plasmid DNA by nanoparticles improves the DNA bioavailability, for instance in intramuscular administration, by localizing the DNA in the muscle tissue. Extracellular sustained release of the DNA may lead to more prolonged transgene expression. The present study describes a novel controlled gene delivery system based on a water soluble and biodegradable polyphosphoester, poly(2-aminoethyl propylene phosphate) (PPE-EA). The polymer degraded in PBS at 37°C through the cleavage of the backbone phosphate bonds, and it was synthesized with a relative high molecular weight to ensure a suitable hydrolytic stability as a gene carrier. The tissue response and cytotoxicity study demonstrated a better tissue compatibility of PPE-EA in mouse muscle compared with commonly used polyethylenimine and poly-L-lysine. PPE-EA condensed DNA efficiently and protected DNA from nuclease and serum degradation. Sustained release of plasmid was achieved from PPE-EA/DNA complexes as a result of PPE-EA degradation. The DNA release profiles appear to be predominantly controlled by carrier degradation and the release rate of plasmid could be adjusted by varying the charge ratio of PPE-EA to DNA. At an N/P (amino to phosphate groups) ratio of 1, a 46% burst was observed for the first day, followed by about 4% release per day (24 μg DNA/day/mg of complex) for 12 days. Higher charge ratios reduced both the DNA release rate and the burst effect. The released DNA retained its structural and functional integrity. Intramuscular injection of PPE-EA-p43-LacZ complexes at N/P ratios of 0.5 and 1 resulted in enhanced β-galactosidase expression in anterior tibialis muscle in Balb/c mice, as compared with naked DNA injections. Similarly, PPE-EA/IFNα2b DNA complexes generated an increased systemic level of interferon-α2b in mouse serum following intramuscular injection, as compared with naked DNA injection.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1038/sj.gt.3301794
dc.sourceScopus
dc.subjectBiodegradable polymer
dc.subjectGene delivery
dc.subjectPolyphosphoester
dc.subjectSustained released
dc.subjectTissue compatibility
dc.typeArticle
dc.contributor.departmentMATERIALS SCIENCE
dc.description.doi10.1038/sj.gt.3301794
dc.description.sourcetitleGene Therapy
dc.description.volume9
dc.description.issue18
dc.description.page1254-1261
dc.description.codenGETHE
dc.identifier.isiut000177853900008
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