Document Detail

Effect of chemically modified IL-13 short interfering RNA on development of airway hyperresponsiveness in mice.
MedLine Citation:
PMID:  17936889     Owner:  NLM     Status:  MEDLINE    
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.
Tricia N Lively; Karl Kossen; Annette Balhorn; Toshiyuki Koya; Shawn Zinnen; Katsuyuki Takeda; Joseph J Lucas; Barry Polisky; Ivan M Richards; Erwin W Gelfand
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-10-22
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  121     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-21     Completed Date:  2008-02-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  88-94     Citation Subset:  AIM; IM    
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
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MeSH Terms
Bone Marrow Cells
Bronchial Hyperreactivity / etiology,  therapy*
Disease Models, Animal
Genes, Reporter
Interleukin-13 / genetics,  metabolism*
Mast Cells
Mice, Inbred BALB C
RNA Interference*
RNA, Small Interfering / chemical synthesis,  genetics,  metabolism,  therapeutic use*
Specific Pathogen-Free Organisms
Treatment Outcome
Grant Support
Reg. No./Substance:
0/Interleukin-13; 0/RNA, Small Interfering

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