Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration.
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.
Interdisciplinary Nanoscience Center, Arhus University, Arhus, Denmark.
Sys Zoffmann
SZ
Glud
Jesper B
JB
Bramsen
Frederik
F
Dagnaes-Hansen
Jesper
J
Wengel
Kenneth Alan
KA
Howard
Jens R
JR
Nyengaard
Jørgen
J
Kjems
D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D048271:Chitosan / Q000378:metabolism; D004337:Drug Carriers; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053758:Nanoparticles; D009841:Oligonucleotides; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D020545:Respiratory Mucosa / Q000378:metabolism*
D004337:Drug Carriers; D009841:Oligonucleotides; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; C477371:locked nucleic acid; D049452:Green Fluorescent Proteins; D048271:Chitosan