Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration

Sys Zoffmann Glud; Jesper B Bramsen; Frederik Dagnaes-Hansen; Jesper Wengel; Kenneth Alan Howard; Jens R Nyengaard; Jørgen Kjems

doi:10.1089/oli.2008.0175

Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration

Sys Zoffmann Glud, Jesper B Bramsen, Frederik Dagnaes-Hansen, Jesper Wengel, Kenneth Alan Howard, Jens R Nyengaard, Jørgen Kjems

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

45 Citations (Scopus)

Abstract

The use of systemic siRNA therapeutics for RNA interference-mediated silencing of disease genes is limited by serum instability and inadequate biodistribution. We have previously reported on the EGFP gene silencing effect of chitosan/siRNA nanoparticles in the bronchoepithelium of mice lungs following intranasal delivery and improved serum stability and reduced off-targeting effects in vitro by incorporation of locked nucleic acid (LNA). In this study, we examine the pulmonary gene silencing effect of siLNAs targeting enhanced-green-fluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and upon intranasal delivery of either naked siLNA or chitosan/siLNA nanoparticles. We show that naked siLNA administered intravenously efficiently reduces the EGFP protein expression. A similar effect is obtained with intranasal delivery of chitosan nanoparticles containing siLNA whereas intranasally instilled naked siLNA did not cause a knockdown.

Original language	English
Journal	Oligonucleotides
Volume	19
Issue	2
Pages (from-to)	163-8
Number of pages	5
ISSN	1545-4576
DOIs	https://doi.org/10.1089/oli.2008.0175
Publication status	Published - 2009

Keywords

Animals
Bronchi
Chitosan
Drug Carriers
Gene Silencing
Green Fluorescent Proteins
Injections, Intravenous
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nanoparticles
Oligonucleotides
RNA, Small Interfering
Respiratory Mucosa

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10.1089/oli.2008.0175

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title = "Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration",

abstract = "The use of systemic siRNA therapeutics for RNA interference-mediated silencing of disease genes is limited by serum instability and inadequate biodistribution. We have previously reported on the EGFP gene silencing effect of chitosan/siRNA nanoparticles in the bronchoepithelium of mice lungs following intranasal delivery and improved serum stability and reduced off-targeting effects in vitro by incorporation of locked nucleic acid (LNA). In this study, we examine the pulmonary gene silencing effect of siLNAs targeting enhanced-green-fluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and upon intranasal delivery of either naked siLNA or chitosan/siLNA nanoparticles. We show that naked siLNA administered intravenously efficiently reduces the EGFP protein expression. A similar effect is obtained with intranasal delivery of chitosan nanoparticles containing siLNA whereas intranasally instilled naked siLNA did not cause a knockdown.",

keywords = "Animals, Bronchi, Chitosan, Drug Carriers, Gene Silencing, Green Fluorescent Proteins, Injections, Intravenous, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nanoparticles, Oligonucleotides, RNA, Small Interfering, Respiratory Mucosa",

author = "Glud, {Sys Zoffmann} and Bramsen, {Jesper B} and Frederik Dagnaes-Hansen and Jesper Wengel and Howard, {Kenneth Alan} and Nyengaard, {Jens R} and J{\o}rgen Kjems",

year = "2009",

doi = "10.1089/oli.2008.0175",

language = "English",

volume = "19",

pages = "163--8",

journal = "Oligonucleotides",

issn = "1545-4576",

publisher = "Mary Ann Liebert Inc.",

number = "2",

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Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration. / Glud, Sys Zoffmann ; Bramsen, Jesper B; Dagnaes-Hansen, Frederik et al.
In: Oligonucleotides, Vol. 19, No. 2, 2009, p. 163-8.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration

AU - Glud, Sys Zoffmann

AU - Bramsen, Jesper B

AU - Dagnaes-Hansen, Frederik

AU - Wengel, Jesper

AU - Howard, Kenneth Alan

AU - Nyengaard, Jens R

AU - Kjems, Jørgen

PY - 2009

Y1 - 2009

N2 - The use of systemic siRNA therapeutics for RNA interference-mediated silencing of disease genes is limited by serum instability and inadequate biodistribution. We have previously reported on the EGFP gene silencing effect of chitosan/siRNA nanoparticles in the bronchoepithelium of mice lungs following intranasal delivery and improved serum stability and reduced off-targeting effects in vitro by incorporation of locked nucleic acid (LNA). In this study, we examine the pulmonary gene silencing effect of siLNAs targeting enhanced-green-fluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and upon intranasal delivery of either naked siLNA or chitosan/siLNA nanoparticles. We show that naked siLNA administered intravenously efficiently reduces the EGFP protein expression. A similar effect is obtained with intranasal delivery of chitosan nanoparticles containing siLNA whereas intranasally instilled naked siLNA did not cause a knockdown.

AB - The use of systemic siRNA therapeutics for RNA interference-mediated silencing of disease genes is limited by serum instability and inadequate biodistribution. We have previously reported on the EGFP gene silencing effect of chitosan/siRNA nanoparticles in the bronchoepithelium of mice lungs following intranasal delivery and improved serum stability and reduced off-targeting effects in vitro by incorporation of locked nucleic acid (LNA). In this study, we examine the pulmonary gene silencing effect of siLNAs targeting enhanced-green-fluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and upon intranasal delivery of either naked siLNA or chitosan/siLNA nanoparticles. We show that naked siLNA administered intravenously efficiently reduces the EGFP protein expression. A similar effect is obtained with intranasal delivery of chitosan nanoparticles containing siLNA whereas intranasally instilled naked siLNA did not cause a knockdown.

KW - Animals

KW - Bronchi

KW - Chitosan

KW - Drug Carriers

KW - Gene Silencing

KW - Green Fluorescent Proteins

KW - Injections, Intravenous

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Nanoparticles

KW - Oligonucleotides

KW - RNA, Small Interfering

KW - Respiratory Mucosa

U2 - 10.1089/oli.2008.0175

DO - 10.1089/oli.2008.0175

M3 - Journal article

C2 - 19441893

SN - 1545-4576

VL - 19

SP - 163

EP - 168

JO - Oligonucleotides

JF - Oligonucleotides

IS - 2

ER -

Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration

Abstract

Keywords

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