COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF IKK-B GENE
First Claim
1. A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a human IKK-B gene in a cell, wherein said dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%.
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Abstract
The invention relates to a doable-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the IKK-B gene, comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the IKK-B gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases, caused by the expression or activation of the IKK-B gene using the pharmaceutical composition; and methods for inhibiting the expression of the IKK-B gene in a cell.
32 Citations
16 Claims
- 1. A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a human IKK-B gene in a cell, wherein said dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%.
- 10. A pharmaceutical composition for inhibiting the expression of the IKK-B gene in an organism, comprising a dsRNA and a pharmaceutically acceptable carrier, wherein the dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%, or preferably by at least 40%.
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13. A method for inhibiting the expression of the IKK-B gene in a cell, the method comprising:
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(a) introducing into the cell a double-stranded ribonucleic acid (dsRNA), wherein the dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%, or preferably by at least 40%; and
(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of the IKK-B gene, thereby inhibiting expression of the IKK-B gene in the cell.
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14. A method of treating, preventing or managing inflammation comprising administering to a patient in need of such treatment, prevention or management a therapeutically or prophylactically effective amount of a dsRNA, wherein the dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%, or preferably by at least 40%.
- 15. A vector for inhibiting the expression of the IKK-B gene in a cell, said vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of a dsRNA, wherein one of the strands of said dsRNA is substantially complementary to at least a part of a mRNA encoding IKK-B and wherein said dsRNA is less than 30 base pairs in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, Inhibits the expression of said IKK-B gene by at least 25%, or preferably by at least 40%.
Specification