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US 2009/0275641 A1Published application
RNAi-Mediated Inhibition of RHO Kinase for Treatment of Ocular Disorders
AssigneeAlcon Research, Ltd.
InventorsJon E. Chatterton, Abbot F. Clark
Life of this patent
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Abstract
RNA interference is provided for inhibition of Rho kinase mRNA expression for treating patients with ocular disorders, particularly for treating intraocular pressure, ocular hypertension and glaucoma. Rho kinase mRNA targets include mRNA for ROCK1 and ROCK2.
Claims19
A method of attenuating expression of Rho kinase mRNA of a subject, comprising:
- administering to an eye of 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 antisense strand:
- comprises a ribonucleotide sequence consisting of the base sequence of SEQ ID NO:
- 3, 9-28, or 30-79 with uridine bases substituted for thymidine bases;
- is substantially complementary to the sense strand;
- and
- hybridizes under physiological conditions to a portion of mRNA corresponding to SEQ ID NO:1 or SEQ ID NO:
- 2;
- wherein the interfering RNA directs RISC-mediated cleavage of Rho kinase mRNA, and wherein the expression of Rho kinase mRNA is attenuated thereby.
7 more elements
A method of attenuating expression of Rho kinase mRNA of a subject, comprising:
- administering to an eye of the subject a composition comprising an effective amount of 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 605, 653, 659, 1248, 1562, 1876, 2266, 2474, 2485, 2740, 2808, 2834, 3007, 3146, 3199, 3245, 3379, 3453, 3511, 3513, 3519, 3782, 998, 1132, 1200, 1648, 1674, 1708, or 2077, and the interfering RNA has a region of at least 80% to 100 contiguous complementarity of at least 19 nucleotides with the hybridizing portion of mRNA corresponding to SEQ ID NO:1,
- or
- wherein the single-stranded interfering RNA hybridizes under physiological conditions to a portion of mRNA corresponding to SEQ ID NO:2 comprising nucleotide 1102, 1865, 2000, 2229, 2514, 2584, 2738, 3305, 4111, 4652, 5184, 5187, 5255, 5315, 5439, 5450, 5578, 5579, 5611, 5625, 5795, 6000, 6228, 6264, 584, 1337, 1678, 2773, 2814, 2941, 3357, 3398, 3481, 3633, 3644, 3645, 3767, 3836, 4023, 4097, 5202, or 5440 and the interfering RNA has a region of at least 80% to 100% contiguous complementarity of at least 19 nucleotides with the hybridizing portion of mRNA corresponding to SEQ ID NO:2,
- wherein the interfering RNA directs cleavage of Rho kinase mRNA, and wherein the expression of Rho kinase mRNA is thereby attenuated.
2 more elements
A method of attenuating expression of Rho kinase mRNA in a subject, the method comprising:
- administering to an eye of 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 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 a ribonucleotide sequence consisting of the base sequence of 3, 9-28, or 30-79, with uridine bases substituted for thymidine bases
- wherein the interfering RNA directs RISC-mediated cleavage of Rho kinase mRNA, and wherein the expression of the Rho kinase mRNA is attenuated thereby.
Dependencies are inferred from the claim text.