RNAi-mediated inhibition of spleen tyrosine kinase-related inflammatory conditions

1. 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 (iRNA) having a length of 19 to 49 nucleotides and a pharmaceutically acceptable carrier, the interfering RNA comprising a sequence having at least 90% sequence complementarity to, or at least 90% sequence identity with SEQ ID NO: 37 or SEQ ID NO: 38;

wherein the expression of Syk mRNA is attenuated thereby.

2. The method of claim 1 , wherein the composition further comprises a second 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 SEQ ID NO: 37 or SEQ ID NO: 38.

3. The method of claim 1 , wherein the interfering RNA is an shRNA.

4. The method of claim 1 , 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.

5. The method of claim 1 , wherein the interfering RNA is administered via in vivo expression from an expression vector capable of expressing the interfering RNA.

6. The method of claim 1 , wherein the interfering RNA is at least one of an miRNA or an siRNA.

7. A method of treating a Syk-related inflammatory condition in a subject in need thereof, 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, the interfering RNA comprising a sequence having at least 90% sequence complementarity to, or at least 90% sequence identity with SEQ ID NO: 37 or SEQ ID NO: 38;

wherein the Syk-related inflammatory condition is treated thereby.

8. The method of claim 7 , wherein the composition further comprises a second 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 SEQ ID NO: 37 or SEQ ID NO: 38.

9. The method of claim 7 , wherein the interfering RNA is an shRNA.

10. The method of claim 7 , 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.

11. The method of claim 7 , wherein the interfering RNA is administered via in vivo expression from an expression vector capable of expressing the interfering RNA.

12. The method of claim 7 , wherein the interfering RNA is at least one of an miRNA or an siRNA.

13. The method of claim 7 , wherein the subject is a human and the human has a Syk-related inflammatory condition or is at risk of developing a Syk-related inflammatory condition.

14. 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, the interfering RNA comprising:

a sense nucleotide strand and an antisense nucleotide strand, wherein the sense and antisense strands comprise at least 90% complementarity over at least 19 nucleotides;

wherein the antisense strand hybridizes under physiological conditions to a portion of mRNA corresponding to SEQ ID NO: 1 comprising nucleotide 2524;

wherein the expression of Syk mRNA is attenuated thereby.

15. The method of claim 14 , wherein the subject is a human and the human has a Syk-related inflammatory condition or is at risk of developing a Syk-related inflammatory condition.

16. The method of claim 14 , further comprising administering to the subject a second 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 complementarity of at least 19 nucleotides;

wherein the antisense strand of the second interfering RNA hybridizes under physiological conditions to a second portion of mRNA selected from the group consisting of

mRNA corresponding to SEQ ID NO:1 comprising nucleotide 789, 791, 860, 861, 862, 867, 868, 1394, 1436, 1471, 1472, 1535, 1547, 1680, 1738, 1739, 1766, 1880, 1947, 2022, 2036, 2328, 2329, 2473, 2509, 2520, 2524, 2558, or 2613, and,

mRNA corresponding to SEQ ID NO:1 comprising nucleotide 1007, 1698, or 1769.

17. The method of claim 16 , wherein the sense nucleotide strand and the antisense nucleotide strand are connected by a loop nucleotide strand.

18. The method of claim 16 , 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.

19. The method of claim 16 , wherein the interfering RNA is administered via in vivo expression from an expression vector capable of expressing the interfering RNA.

20. A method of treating a Syk-related inflammatory condition in a subject in need thereof, 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, the interfering RNA comprising:

a sense nucleotide strand and an antisense nucleotide strand, wherein the sense and antisense strands comprise at least 90% complementarity over at least 19 nucleotides;

wherein the antisense strand hybridizes under physiological conditions to a portion of mRNA corresponding to SEQ ID NO: 1 comprising nucleotide 2524;

wherein the Syk-related inflammatory condition is treated thereby.

21. The method of claim 20 , wherein the subject is a human and the human has a Syk-related inflammatory condition or is at risk of developing a Syk-related inflammatory condition.

22. The method of claim 20 , further comprising administering to the subject a second 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 complementarity of at least 19 nucleotides;

wherein the antisense strand of the second interfering RNA hybridizes under physiological conditions to a second portion of mRNA selected from the group consisting of

mRNA corresponding to SEQ ID NO:1 comprising nucleotide 789, 791, 860, 861, 862, 867, 868, 1394, 1436, 1471, 1472, 1535, 1547, 1680, 1738, 1739, 1766, 1880, 1947, 2022, 2036, 2328, 2329, 2473, 2509, 2520, 2524, 2558, or 2613, and,

mRNA corresponding to SEQ ID NO:1 comprising nucleotide 1007, 1698, or 1769.

23. The method of claim 22 , wherein the sense nucleotide strand and the antisense nucleotide strand are connected by a loop nucleotide strand.

24. The method of claim 22 , 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.

25. The method of claim 22 , wherein the interfering RNA is administered via in vivo expression from an expression vector capable of expressing the interfering RNA.

26. A method of attenuating expression of Syk mRNA of a subject, comprising: administering to the subject a composition comprising an effective amount of a single-stranded interfering RNA having a length of 19 to 49 nucleotides, and a pharmaceutically acceptable carrier, wherein the single-stranded interfering RNA hybridizes under physiological conditions to a portion of mRNA corresponding to SEQ ID NO: 1 comprising nucleotide 2524;

and the interfering RNA has a region of at least 90% complementarity with the mRNA corresponding to SEQ ID NO: 1;

wherein the expression of Syk mRNA is thereby attenuated.

27. The method of claim 26 , 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.

28. The method of claim 26 , wherein the interfering RNA is administered via in vivo expression from an expression vector capable of expressing the interfering RNA.

29. The method of claim 26 , wherein the interfering RNA is at least one of an miRNA or an siRNA.

30. A method of treating ocular inflammation or conjunctivitis in a subject in need thereof, comprising:

administering to the subject a composition comprising a double stranded siRNA molecule that down regulates expression of a Syk gene via RNA interference,

wherein:

each strand of the siRNA molecule is independently about 19 to about 27 nucleotides in length; and

one strand of the siRNA molecule comprises a nucleotide sequence having substantial complementarity to an mRNA corresponding to SEQ ID NO: 37 or SEQ ID NO: 38 so that the siRNA molecule directs cleavage of the mRNA via RNA interference.

31. The method of claim 30 , 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.

32. The method of claim 30 , wherein the interfering RNA is administered via in vivo expression from an expression vector capable of expressing the interfering RNA.

33. The method of claim 30 , wherein the interfering RNA is an miRNA.

34. The method of claim 30 , wherein each strand of the siRNA molecule is independently about 19 nucleotides to about 25 nucleotides in length or independently about 19 nucleotides to about 21 nucleotides in length.

35. A composition comprising an interfering RNA having a length of 19 to 49 nucleotides, and comprising a nucleotide sequence corresponding to SEQ ID NO: 37 or SEQ ID NO: 38, or a complement thereof; and a pharmaceutically acceptable carrier.

36. The composition of claim 35 , wherein the interfering RNA is at least one of an shRNA, an siRNA, or an miRNA.