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


OBJECTIVE
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.


CONCLUSIONS
These data demonstrate the effectiveness of introducing targeted siRNAs to prevent induction of allergen-induced airway dysfunction and suggest potential therapeutic applications.
Lively
Tricia N
TN
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Kossen
Karl
K
Balhorn
Annette
A
Koya
Toshiyuki
T
Zinnen
Shawn
S
Takeda
Katsuyuki
K
Lucas
Joseph J
JJ
Polisky
Barry
B
Richards
Ivan M
IM
Gelfand
Erwin W
EW
D000818:Animals; D001854:Bone Marrow Cells; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D016896:Treatment Outcome
D018793:Interleukin-13; D034741:RNA, Small Interfering