Effect of chemically modified IL-13 short interfering RNA on development of airway hyperresponsiveness in mice.
J Allergy Clin Immunol
; 121(1): 88-94, 2008 Jan.
Article
de En
| MEDLINE
| ID: mdl-17936889
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Hyperréactivité bronchique
/
Interleukine-13
/
Petit ARN interférent
/
Interférence par ARN
Type d'étude:
Etiology_studies
Limites:
Animals
/
Female
/
Humans
Langue:
En
Journal:
J Allergy Clin Immunol
Année:
2008
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique