Conclusion & References

1 National Institutes of Health. National Heart, Lung, and Blood Institute. Report 1999. http://www.nhlbi.nih.gov/health/prof/lung/asthma/asthstat.pdf

2 Grzela K et al. “Molecular therapy versus standard treatment in allergy (Review).” Int J Mol Med. 14(1), 2004 Jul: 3-22.
 3 Novina CD et al. Nature. Vol 430, July 2004: 161-164.

4 Amarzguioui, M. “Approaches for chemically synthesized siRNA and vector-mediated RNAi.” FEBS Lett. 2005 Oct 31;579(26):5974-81.  5 Maddox L, Schwartz DA. “The pathophysiology of asthma.” Annual Review of Medicine. Vol. 53, 2002: 477-498.

6 Janeway, Charles A. et al. Immunobiology. 6th Edition. New York: Garland Science, 2005.

7 Popescu FD. “Antisense- and RNA interference-based therapeutic strategies in allergy.” J Cell Mol Med. 2005 Oct-Dec;9(4):840-53.

8 Chatila TA. “Interleukin-4 receptor signaling pathways in asthma pathogenesis.” Trends Mol Med. 2004 Oct;10(10):493-9.

9 Heinonen JE. “Silencing of Bruton's tyrosine kinase (Btk) using short interfering RNA duplexes (siRNA).” FEBS Lett. 2002 Sep 11 527(1-3):274-8.

10Guo J. et al. “Dissecting role of regulatory factors in NF-kappaB pathway with siRNA.” Acta Pharmacol Sin. 2005 Jul;26(7):780-8.

11 Xie FY. “Harnessing in vivo siRNA delivery for drug discovery and therapeutic development.” Drug Discov Today. 2006 Jan;11(1-2):67-73.

12 Soutschek J. et al. “Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs.” Nature. 2004 Nov 11;432(7014):173-8.

13 Sorensen DR et al. “Gene silencing by systemic delivery of synthetic siRNAs in adult mice.” J Mol Biol. 2003 Apr 4;327(4):761-6.

14 SIRNA Therapeutics website. http://www.sirna.com/wt/page/index

15 Davidson BL et al. “Molecular medicine for the brain: silencing of disease genes with RNA interference.” Lancet Neurol. 2004 Mar;3(3):145-9.  16 Leung RK. “RNA interference: from gene silencing to gene-specific therapeutics.” Pharmacol Ther. 2005 Aug;107(2):222-39.
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17 Xia, H., Mao, Q., Paulson, H. L., & Davidson, B. L. (2002). “SiRNA mediated gene silencing in vitro and in vivo.” Nat Biotechnol 20(10), 1006–1010.

Asthma is a chronic inflammatory disease of the airways marked by reversible airway obstruction, chronic airway inflammation, airway hyperreactivity, and airway remodeling. These inflammatory events are mediated by activation of mast cells, which cause release of inflammatory molecules that attract T helper cells and eosinophils to the area. In turn, the T helper cells (which commit to a Th2 form) secrete cytokines (IL-4 and IL-13) that perpetuate the inflammatory response. RNA interference is a gene silencing tactic by introduction of dsRNA complementary to the mRNA of interest. In treating asthma, various mediators of the inflammatory cascade, including cytokines, chemokines and their receptors, adhesion molecules, cell membrane receptors, protein kinases, and transcription factors, could be targets for RNAi therapy. RNAi can be delivered by chemical modification of the oligonucleotide itself, via non-viral carriers like liposomes, or via viral vectors like adenovirus.