Effect of chemically modified IL-13 short interfering RNA on development of airway hyperresponsiveness in mice

Autor: Karl Kossen, Toshiyuki Koya, Erwin W. Gelfand, Barry Polisky, Joseph J. Lucas, Shawn Zinnen, Tricia N. Lively, Ivan Richards, Annette Balhorn, Katsuyuki Takeda
Rok vydání: 2008
Předmět:
Small interfering RNA
AHR
Airway hyperresponsiveness
AHR
Cell
Mice
0302 clinical medicine
Airway resistance
Genes
Reporter
dsRNA
Double-stranded RNA
RNA interference
Immunology and Allergy
Mast Cells
RNA
Small Interfering
siRNA
Short interfering RNA
Mice
Inbred BALB C
0303 health sciences
Interleukin-13
OVA
Ovalbumin
Specific Pathogen-Free Organisms
Cell biology
RNA silencing
Treatment Outcome
medicine.anatomical_structure
IL-13
HE
Hematoxylin-eosin
Female
RNA Interference
Bronchial Hyperreactivity
eosinophilia
BAL
Bronchoalveolar lavage
GFP
Green fluorescence protein
RL
Lung resistance
Immunology
Bone Marrow Cells
Biology
Article
MCh
Methacholine
03 medical and health sciences
Immune system
PAS
Periodic acid-Schiff
medicine
Animals
Humans
Gene silencing
BMMC
Bone marrow–derived mast cell
030304 developmental biology
Reporter gene
Disease Models
Animal
siRNA
030215 immunology
Zdroj: The Journal of Allergy and Clinical Immunology
ISSN: 0091-6749
DOI: 10.1016/j.jaci.2007.08.029
Popis: Background RNA interference is an endogenous cellular mechanism in which short interfering RNAs (siRNAs) direct the sequence specific degradation of a target mRNA. siRNAs can be synthesized with chemical modifications to increase stability and reduce double-stranded RNA–induced immune responses without affecting their ability to elicit degradation of target mRNA. Objectives This study examined the use of chemically modified siRNAs in a mouse model of allergen-induced airway hyperresponsiveness. Methods Chemically modified siRNAs were designed and screened in a cell-based reporter assay. The most potent siRNAs were then screened in bone marrow–derived mast cells to demonstrate efficacy in primary cells. Results A candidate siRNA was formulated and administered to sensitized mice just before airway challenge with allergen. Administration of the siRNA was shown to reduce airway resistance significantly in sensitized and challenged mice by 60%, whereas a control siRNA had no effect. Conclusion These data demonstrate the effectiveness of introducing targeted siRNAs to prevent induction of allergen-induced airway dysfunction and suggest potential therapeutic applications.
Databáze: OpenAIRE
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