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J Control Release. 2010 Jan 4;141(1):77-84. doi: 10.1016/j.jconrel.2009.08.022. Epub 2009 Aug 29.

Effect of innate glutathione levels on activity of redox-responsive gene delivery vectors.

Author information

1
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.

Abstract

Redox-responsive polyplexes represent a promising class of non-viral gene delivery vectors. The reducible disulfide bonds in the polyplexes undergo intracellular reduction owing to the presence of high concentrations of reduced glutathione (GSH). Available evidence suggests improved transfection activity of redox-sensitive polyplexes upon artificial modulation of intracellular GSH. This study investigates the effect of innate differences in GSH concentration in a panel of human pancreatic cancer cell lines on activity of reducible polyplexes of the four major classes of nucleic acid therapeutics: plasmid DNA (pDNA), messenger RNA (mRNA), antisense oligodeoxynucleotides (AON) and siRNA. In general, reducible polyplexes of linear poly(amido amines) (PAA) show improved activity compared to non-reducible polyplexes of PAA. Results demonstrate that increased GSH levels are associated with improved transfection of mRNA polyplexes but no clear trend is observed for pDNA, AON and siRNA polyplexes.

PMID:
19720098
PMCID:
PMC2791204
DOI:
10.1016/j.jconrel.2009.08.022
[Indexed for MEDLINE]
Free PMC Article

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