Antisense oligonucleotides to Syk kinase: a novel therapeutic approach for respiratory disorders.
The non-receptor protein tyrosine kinase Syk plays a critical role in intracellular signaling in the inflammatory response. Specific inhibition of Syk using aerosolized antisense delivered in liposome complexes can significantly decrease inflammatory responses in the airways in experimental animal models. Thus, it is tempting to examine local application of Syk antisense for the treatment of inflammatory respiratory diseases as asthma. However, evidence that Syk kinase is more widely distributed in different cell types than previously recognized, as well as its potential involvement in cell differentiation, adhesion and proliferation, dictates that the precise cellular targets for antisense therapy in the airways must be determined. Given the critical role of Syk in intracellular signaling in inflammatory responses, Syk antisense oligonucleotides (InKine Pharmaceutical Co Inc) may prove useful as anti-inflammatory therapy in disorders such as asthma.
Ulanova
Marina
M
Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada.
Puttagunta
Lakshmi
L
Kim
Moo-Kyung
MK
Schreiber
Alan D
AD
Befus
A Dean
AD
D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D004792:Enzyme Precursors / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000072377:Syk Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase