RNAi-MEDIATED INHIBITION OF SPLEEN TYROSINE KINASE-RELATED INFLAMMATORY CONDITIONS

Abstract

RNA interference is provided for inhibition of spleen tyrosine kinase (Syk) mRNA expression, in particular, for treating patients having a Syk-related inflammatory condition or at risk of developing a Syk-related inflammatory condition such as allergic conjunctivitis, ocular inflammation, dermatitis, rhinitis, asthma, allergy, or mast-cell disease.

1 . A composition comprising an interfering RNA having a length of 19 to 49 nucleotides, and comprising a region of at least 13 contiguous nucleotides having at least 90% sequence complementarity to, or at least 90% sequence identity with, the penultimate 13 nucleotides of the 3′ end of any one of SEQ ID NO:44-47. 
     
     
         2 . The composition of  claim 1 , wherein the interfering RNA comprises an shRNA, an siRNA, or an miRNA. 
     
     
         3 . The composition of  claim 1  wherein the interfering RNA has at least one 3′ overhang. 
     
     
         4 . The composition of  claim 1  wherein the interfering RNA has at least one 5′ overhang. 
     
     
         5 . The composition of  claim 1  wherein the interfering RNA has one or more chemically modified nucleotide. 
     
     
         6 . The composition of  claim 1  wherein the interfering RNA has one or more non-phosphodiester linkages. 
     
     
         7 . The composition of  claim 1  further comprising a pharmaceutically acceptable carrier. 
     
     
         8 . A method of attenuating expression of Syk mRNA of a subject, comprising:
 administering to the subject a composition comprising an effective amount of interfering RNA having a length of 19 to 49 nucleotides and a pharmaceutically acceptable carrier, wherein the interfering RNA comprises region of at least 13 contiguous nucleotides having at least 90% sequence complementarity to, or at least 90% sequence identity with, the penultimate 13 nucleotides of the 3′ end of any one of SEQ ID NO:44-47,   wherein the expression of Syk mRNA is attenuated thereby.   
     
     
         9 . The method of  claim 8 , wherein the interfering RNA comprises an shRNA, an siRNA, or an miRNA. 
     
     
         10 . The method of  claim 8  wherein the interfering RNA has at least one 3′ overhang. 
     
     
         11 . The method of  claim 8  wherein the interfering RNA has at least one 5′ overhang. 
     
     
         12 . The method of  claim 8  wherein the interfering RNA has one or more chemically modified nucleotide. 
     
     
         13 . The method of  claim 8  wherein the interfering RNA has one or more non-phosphodiester linkages. 
     
     
         14 . The method of  claim 8 , wherein the composition is administered via an aerosol, buccal, dermal, intradermal, inhaling, intramuscular, intranasal, intraocular, intrapulmonary, intravenous, intraperitoneal, nasal, ocular, oral, otic, parenteral, patch, subcutaneous, sublingual, topical, or transdermal route. 
     
     
         15 . A composition comprising an interfering RNA having a length of 19 to 49 nucleotides, and comprising a sense nucleotide strand, an antisense nucleotide strand, and a region of at least near-perfect contiguous complementarity of at least 19 nucleotides; wherein the antisense strand hybridizes under physiological conditions to a portion of mRNA selected from the group consisting of mRNA corresponding to SEQ ID NO: 1 comprising nucleotide 642, 1009, 1273, or 1533. 
     
     
         16 . The composition of  claim 15 , wherein the interfering RNA comprises an shRNA, an siRNA, or an miRNA. 
     
     
         17 . The composition of  claim 15  wherein the interfering RNA has at least one 3′ and/or 5′ overhang. 
     
     
         18 . The composition of  claim 15  wherein the interfering RNA has one or more chemically modified nucleotide. 
     
     
         19 . The composition of  claim 15  wherein the interfering RNA has one or more non-phosphodiester linkages. 
     
     
         20 . The composition of  claim 15  further comprising a pharmaceutically acceptable carrier.