US2008293659A1PendingUtilityA1

FC gamma RIIA-specific nucleic acid interference

27
Individually held — no corporate assignee on recordPriority: Nov 14, 2003Filed: Mar 25, 2008Published: Nov 27, 2008
Est. expiryNov 14, 2023(expired)· nominal 20-yr term from priority
Inventors:Diana BeardsleyBing-Guan Chen
C12Y 207/10001C12N 2310/14C12N 15/1137
27
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Claims

Abstract

The present invention provides methods and compositions for attenuating expression of FcγRIIA. In general, the described methodology involves the use of RNAi constructs that are targeted to a FcγRIIA mRNA sequence.

Claims

exact text as granted — not AI-modified
1 . An RNAi construct for inhibiting the expression of FcγRIIA, comprising
 (a) an antisense polynucleotide strand that hybridizes to at least a portion of a FcγRIIA transcript and inhibits FcγRIIA expression; and   (b) a sense polynucleotide that hybridizes to said antisense polynucleotide.   
     
     
         2 . The RNAi construct of  claim 1 , wherein the double-stranded nucleic acid is a hairpin nucleic acid. 
     
     
         3 . The RNAi construct of  claim 1 , wherein the antisense strand and the sense strand form a double helix of about 19 to about 30 base pairs in length. 
     
     
         4 . The RNAi construct of  claim 1 , wherein the antisense polynucleotide strand is complementary to a sequence of the human FcγRIIA mRNA of SEQ ID NO:1. 
     
     
         5 . The RNAi construct of  claim 4 , wherein the RNA antisense polynucleotide strand is complementary to at least 7 nucleotides of a sequence selected from the group consisting of: SEQ ID Nos. 4-13. 
     
     
         6 . The RNAi construct of  claim 4 , wherein the RNA antisense polynucleotide strand consists of a sequence that is complementary to a sequence selected from the group consisting of: SEQ ID Nos. 4-13. 
     
     
         7 . The RNAi construct of  claim 4 , wherein greater than 50% of the nucleotides of the antisense strand are RNA. 
     
     
         8 . The RNAi construct of  claim 4 , wherein the antisense strand comprises one or more modifications selected from the group consisting of:
 (a) a modification to the sugar-phosphate backbone;   (b) a modification to a base portion of a nucleotide; and   (c) a conjugated hydrophobic moiety.   
     
     
         9 . The double-stranded nucleic acid of  claim 4 , wherein the sense strand comprises one or more modifications selected from the group consisting of:
 (a) a modification to the sugar-phosphate backbone;   (b) a modification to a base portion of a nucleotide; and   (c) a conjugated hydrophobic moiety.   
     
     
         10 . A pharmaceutical preparation for delivery of an RNAi construct to an organism, the composition comprising a pharmaceutically acceptable carrier and an RNAi construct that inhibits expression of FcγRIIA. 
     
     
         11 . The pharmaceutical preparation of  claim 10 , wherein the RNAi construct comprises:
 (a) an antisense polynucleotide strand that hybridizes to at least a portion of a FcγRIIA transcript and inhibits FcγRIIA expression; and   (b) a sense polynucleotide that hybridizes to said antisense polynucleotide.   
     
     
         12 . The pharmaceutical preparation of  claim 11 , wherein the antisense polynucleotide strand is complementary to at least 7 nucleotides of a sequence selected from the group consisting of: SEQ ID Nos. 4-13. 
     
     
         13 . The pharmaceutical preparation of  claim 11 , wherein the antisense polynucleotide strand consists of a sequence that is complementary to a sequence selected from the group consisting of: SEQ ID Nos. 4-13. 
     
     
         14 . The pharmaceutical preparation of  claim 11 , wherein greater than 50% of the nucleotides of the antisense strand are RNA. 
     
     
         15 . The pharmaceutical preparation of  claim 11 , wherein the antisense strand comprises one or more modifications selected from the group consisting of:
 (a) a modification to the sugar-phosphate backbone;   (b) a modification to a base portion of a nucleotide; and   (c) a conjugated hydrophobic moiety.   
     
     
         16 . The pharmaceutical preparation of  claim 11 , wherein the sense strand comprises one or more modifications selected from the group consisting of:
 (a) a modification to the sugar-phosphate backbone;   (b) a modification to a base portion of a nucleotide; and   (c) a conjugated hydrophobic moiety.   
     
     
         17 . The pharmaceutical preparation of  claim 10 , wherein the preparation is suitable for administration by inhalation. 
     
     
         18 . A method for decreasing expression of FcγRIIA in a cell, the method comprising contacting the cell with an RNAi construct which comprises:
 (a) an antisense polynucleotide strand that hybridizes to at least a portion of a FcγRIIA transcript and inhibits FcγRIIA expression; and   (b) a sense polynucleotide that hybridizes to said antisense polynucleotide.   
     
     
         19 . The method of  claim 18 , wherein the antisense polynucleotide strand is complementary to a sequence of the human FcγRIIA mRNA of SEQ ID NO: 1. 
     
     
         20 . The method of  claim 18 , wherein the antisense polynucleotide strand is complementary to at least 7 nucleotides of a sequence selected from the group consisting of: SEQ ID Nos. 4-13. 
     
     
         21 . The method of  claim 18 , wherein the antisense polynucleotide strand consists of a sequence that is complementary to a sequence selected from the group consisting of: SEQ ID Nos. 4-13. 
     
     
         22 . A method for decreasing expression of FcγRIIA in one or more cells of an individual, the method comprising administering to the individual a composition comprising an RNAi construct which comprises:
 (a) an antisense polynucleotide strand that hybridizes to at least a portion of a FcγRIIA transcript and inhibits FcγRIIA expression; and   (b) a sense polynucleotide that hybridizes to said antisense polynucleotide.   
     
     
         23 . The method of  claim 22 , wherein the antisense polynucleotide strand is complementary to a sequence of the human FcγRIIA mRNA of SEQ ID NO: 1. 
     
     
         24 . The method of  claim 22 , wherein the antisense polynucleotide strand is complementary to at least 7 nucleotides of a sequence selected from the group consisting of: SEQ ID Nos. 4-13. 
     
     
         25 . The method of  claim 22 , wherein the antisense polynucleotide strand consists of a sequence that is complementary to a sequence selected from the group consisting of: SEQ ID Nos. 4-13. 
     
     
         26 . The method of  claim 22 , wherein the individual has a condition associated with excess Fc receptor activity. 
     
     
         27 . The method of  claim 22 , wherein the individual has asthma or experiences symptoms associated with asthma or allergic rhinitis. 
     
     
         28 . The method of  claim 27 , wherein the composition comprising the RNAi construct is administered by a mode selected from the group consisting of: inhalation, topical and intravenous. 
     
     
         29 . The method of  claim 22 , wherein the individual has an immune cytopenia or a heparin induced thrombocytopenia. 
     
     
         30 . The RNAi construct of  claim 1 , wherein the construct does not substantially inhibit FcγRIIB expression.

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