Compounds for modulating fc-epsilon-ri-beta expression and uses thereof

Abstract

Methods for treating diseases and conditions mediated by the high affinity IgE receptor (FcεRI). Antisense oligomers for modulating splicing of mRNA encoding the FcεRIβ protein, thereby down-regulating cell-surface expression of FcεRI, and uses of the antisense oligomers for inhibiting mast cell degranulation, cytokine release, migration, and proliferation.

1 - 34 . (canceled) 
     
     
         35 . A method of modulating splicing of FcεRIβ mRNA in cells or tissues, comprising contacting the cells or tissues with an antisense oligomer comprising 10 to 50 linked nucleosides, wherein the antisense oligomer is targeted to a region of a pre-mRNA encoding a FcεRIβ protein, and wherein the targeted region comprises sequences involved in splicing of the FcεRIβ-encoding pre-mRNA and/or an expression vector coding the same. 
     
     
         36 . A method of reducing cell surface expression of FcεRI protein in a cell, comprising contacting the cell with. 
     
     
         37 - 38 . (canceled) 
     
     
         39 . A method of modulating cytokine release, comprising contacting a cytokine-producing cell with an antisense oligomer comprising 10 to 50 linked nucleosides, wherein the antisense oligomer is targeted to a region of a pre-mRNA encoding a FcεRIβ protein, and wherein the targeted region comprises sequences involved in splicing of the FcεRIβ-encoding pre-mRNA and/or an expression vector coding the same. 
     
     
         40 . The method of  claim 35 , wherein the method is performed in an individual. 
     
     
         41 - 48 . (canceled) 
     
     
         49 . The method of  claim 40 , wherein the individual is a human, a mouse, a dog, a cat, or a horse. 
     
     
         50 . The method of  claim 35 , wherein the antisense oligomer is a morpholino oligomer. 
     
     
         51 . The method of  claim 35 , wherein the targeted region is selected from the group consisting of an exon 2 or 3 sequence, an exon 2 or 3 slice acceptor sequence, an exon 2 or 3 splice enhancer sequence, an exon 2 or 3 splice branch point sequence, and an exon 2 or 3 polypyrimidine tract of the pre-mRNA encoding the FcεRIβ protein. 
     
     
         52 . The method of  claim 51 , wherein hybridization of the antisense oligomer to the pre-mRNA encoding the FcεRIβ protein results in production of a mature MS4A2 mRNA molecule that lacks at least a portion of exon 2 and/or exon 3. 
     
     
         53 . The method of  claim 35 , wherein the antisense oligomer comprises a nucleotide sequence that is identical over its full length to a sequence selected from the group consisting of SEQ ID NOs: 243, 669, 670, 687, 943, and 968. 
     
     
         54 . The method of  claim 35 , wherein the antisense oligomer is an antisense RNA molecule. 
     
     
         55 . The method of  claim 54 , wherein the antisense RNA molecule comprises a modification selected from the group consisting of a nucleoside modification, an internucleoside modification, a sugar modification, a sugar-internucleoside linkage modification, and combinations thereof. 
     
     
         56 . The method of  claim 55 , wherein the modification increases degradation of a target sequence by a ribonuclease when the antisense RNA molecule hybridizes to the target sequence in the presence of the ribonuclease. 
     
     
         57 . The method of  claim 39 , wherein the antisense oligomer is a morpholino oligomer. 
     
     
         58 . The method of  claim 39 , wherein the method is performed in an individual. 
     
     
         59 . The method of  claim 59 , wherein the individual is a human, a mouse, a dog, a cat, or a horse.