A Unique Gene-Silencing Approach, Using an Intelligent RNA Expression Device (iRed), Results in Minimal Immune Stimulation When Given by Local Intrapleural Injection in Malignant Pleural Mesothelioma

We have recently introduced an intelligent RNA expression device (iRed), comprising the minimum essential components needed to transcribe short hairpin RNA (shRNA) in cells. Use of iRed efficiently produced shRNA molecules after transfection into cells and alleviated the innate immune stimulation fo...

Full description

Saved in:
Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2020-04, Vol.25 (7), p.1725
Main Authors: Ando, Hidenori, Saito-Tarashima, Noriko, Lila, Amr S Abu, Kinjo, Nozomi, Shimizu, Taro, Ishima, Yu, Minakawa, Noriaki, Ishida, Tatsuhiro
Format: Article
Language:English
Subjects:
Animals
cationic liposomes
Cell Line, Tumor
Deoxyribonucleic acid
Disease Models, Animal
DNA
Gene Expression
Gene Silencing
Humans
Immunity, Innate - genetics
Immunomodulation - genetics
Injection
innate immunity
intelligent RNA expression device (iRed)
Interleukin 6
Intravenous administration
Liposomes
Mesothelioma
Mesothelioma, Malignant - genetics
Mice
Molecular weight
Plasmids
Pleural Neoplasms - genetics
Polyethylene glycol
Ratios
RNA Interference
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
RNA-mediated interference
shRNA
Stimulation
Transfection
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We have recently introduced an intelligent RNA expression device (iRed), comprising the minimum essential components needed to transcribe short hairpin RNA (shRNA) in cells. Use of iRed efficiently produced shRNA molecules after transfection into cells and alleviated the innate immune stimulation following intravenous injection. To study the usefulness of iRed for local injection, the engineered iRed encoding luciferase shRNA (Luc iRed), complexed with cationic liposomes (Luc iRed/liposome-complexes), was intrapleurally injected into an orthotopic mesothelioma mouse model. Luc iRed/liposome-complexes markedly suppressed the expression of a luciferase marker gene in pleurally disseminated mesothelioma cells. The suppressive efficiency was correlated with the expression level of shRNA within the mesothelioma cells. In addition, intrapleural injection of iRed/liposome-complexes did not induce IL-6 production in the pleural space and consequently in the blood compartment, although plasmid DNA (pDNA) or dsDNA (the natural construct for iRed) in the formulation did. Local delivery of iRed could augment the in vivo gene silencing effect without eliciting pronounced innate immune stimulation. Our results might hold promise for widespread utilization of iRed as an RNAi-based therapeutic for intracelial malignant cancers.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules25071725