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

Devika S. Manickam, Jing Li, David A. Putt, Qing Hui Zhou, Chao Wu, Lawrence H. Lash, David Oupický

Research output: Contribution to journalArticle

80 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalJournal of Controlled Release
Volume141
Issue number1
DOIs
StatePublished - Jan 4 2010

Fingerprint

Oligodeoxyribonucleotides
Small Interfering RNA
Oxidation-Reduction
Transfection
Glutathione
Plasmids
Antisense DNA
Messenger RNA
Pancreatic Neoplasms
Disulfides
Nucleic Acids
Genes
Amines
Cell Line
DNA
Therapeutics

Keywords

  • Glutathione
  • Non-viral gene delivery
  • Pancreatic cancer
  • Reducible polyplexes
  • Transfection

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Effect of innate glutathione levels on activity of redox-responsive gene delivery vectors. / Manickam, Devika S.; Li, Jing; Putt, David A.; Zhou, Qing Hui; Wu, Chao; Lash, Lawrence H.; Oupický, David.

In: Journal of Controlled Release, Vol. 141, No. 1, 04.01.2010, p. 77-84.

Research output: Contribution to journalArticle

Manickam, Devika S. ; Li, Jing ; Putt, David A. ; Zhou, Qing Hui ; Wu, Chao ; Lash, Lawrence H. ; Oupický, David. / Effect of innate glutathione levels on activity of redox-responsive gene delivery vectors. In: Journal of Controlled Release. 2010 ; Vol. 141, No. 1. pp. 77-84.
@article{e41cd4079d134d41b58c0fba855de68d,
title = "Effect of innate glutathione levels on activity of redox-responsive gene delivery vectors",
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.",
keywords = "Glutathione, Non-viral gene delivery, Pancreatic cancer, Reducible polyplexes, Transfection",
author = "Manickam, {Devika S.} and Jing Li and Putt, {David A.} and Zhou, {Qing Hui} and Chao Wu and Lash, {Lawrence H.} and David Oupick{\'y}",
year = "2010",
month = "1",
day = "4",
doi = "10.1016/j.jconrel.2009.08.022",
language = "English (US)",
volume = "141",
pages = "77--84",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Effect of innate glutathione levels on activity of redox-responsive gene delivery vectors

AU - Manickam, Devika S.

AU - Li, Jing

AU - Putt, David A.

AU - Zhou, Qing Hui

AU - Wu, Chao

AU - Lash, Lawrence H.

AU - Oupický, David

PY - 2010/1/4

Y1 - 2010/1/4

N2 - 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.

AB - 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.

KW - Glutathione

KW - Non-viral gene delivery

KW - Pancreatic cancer

KW - Reducible polyplexes

KW - Transfection

UR - http://www.scopus.com/inward/record.url?scp=70849130936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70849130936&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2009.08.022

DO - 10.1016/j.jconrel.2009.08.022

M3 - Article

C2 - 19720098

AN - SCOPUS:70849130936

VL - 141

SP - 77

EP - 84

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 1

ER -