RNAi-mediated inhibition of HIF1A for treatment of ocular angiogenesis
First Claim
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1. A method of attenuating expression of HIF1A 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, an antisense nucleotide strand, and a region of at least near-perfect contiguous complementarity of at least 19 nucleotides;
wherein the antisense strand hybridizes under physiological conditions to a portion of MRNA corresponding to SEQ ID NO;
1 or SEQ ID NO;
2 and has a region of at least near-perfect contiguous complementarity of at least 19 nucleotides with the hybridizing portion of MRNA corresponding to SEQ ID NO;
1 or SEQ ID NO;
2, respectively, wherein the expression of HIF1A mRNA is attenuated thereby.
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Accused Products
Abstract
RNA interference, is provided for inhibition of HIF1A mRNA expression for treating patients with ocular angiogenesis, particularly for treating retinal edema, diabetic retinopathy, sequela associated with retinal ischemia, posterior segment neovascularization (PSNV), and neovascular glaucoma, and for treating patients at risk of developing such conditions.
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Citations
45 Claims
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1. A method of attenuating expression of HIF1A mRNA of a subject, comprising:
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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, an antisense nucleotide strand, and a region of at least near-perfect contiguous complementarity of at least 19 nucleotides;
wherein the antisense strand hybridizes under physiological conditions to a portion of MRNA corresponding to SEQ ID NO;
1 or SEQ ID NO;
2 and has a region of at least near-perfect contiguous complementarity of at least 19 nucleotides with the hybridizing portion of MRNA corresponding to SEQ ID NO;
1 or SEQ ID NO;
2, respectively,wherein the expression of HIF1A mRNA is attenuated thereby. - View Dependent Claims (2, 3, 4, 5, 6, 7, 20)
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8. A method of treating ocular angiogenesis in a subject in need thereof, comprising:
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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, an antisense nucleotide strand, and a region of at least near-perfect contiguous complementarity of at least 19 nucleotides;
wherein the antisense strand hybridizes under physiological conditions to a portion of mRNA corresponding to SEQ ID NO;
1 or SEQ ID NO;
2, and has a region of at least near-perfect contiguous complementarity of at least 19 nucleotides with the hybridizing portion of mRNA corresponding to SEQ ID NO;
1 or SEQ ID NO;
2, respectively,wherein the ocular angiogenesis is treated thereby. - View Dependent Claims (21, 28, 30, 32)
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9. A method of attenuating expression of HIF1A mRNA of a subject, comprising:
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administering to 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 411, 580, 583, 868, 869, 1099, 1100, 1242, 1302, 1371, 1396, 1559, 1560, 1809, 2085, 2087, 2105, 2138, 2256, 2358, 2422, 2636, 2666, 2743, 2858, 2861, 3135, 3544, 3554, 1943, 1791, 2351, or 1408, and the interfering RNA has a region of at least near-perfect contiguous complementarity of at least 19 nucleotides with the hybridizing portion of mRNA corresponding to SEQ ID NO;
1, orwherein the single-stranded interfering RNA hybridizes under physiological conditions to a portion of mRNA corresponding to SEQ ID NO;
2 comprising nucleotide 2360, 2411, 2420, 2536, 2539, 2545, 2616, 2731, 2734, 3008, or 3427 and the interfering RNA has a region of at least near-perfect contiguous complementarity of at least 19 nucleotides with the hybridizing portion of mRNA corresponding to SEQ ID NO;
2,wherein the expression of HIF1A mRNA is thereby attenuated.
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10. A method of attenuating expression of HIF1A mRNA in a subject, the method comprising:
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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 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 an mRNA corresponding to any one of SEQ ID NO;
3, and SEQ ID NO;
9-SEQ ID NO;
51,wherein the expression of HIFI A mRNA is thereby attenuated. - View Dependent Claims (11, 12, 13, 14, 15, 22, 24, 26)
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16. A method of treating ocular angiogenesis in a subject in need thereof, the method comprising:
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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 an mRNA corresponding to any one of SEQ ID NO;
3, and SEQ ID NO;
9-SEQ ID NO;
51, wherein the ocular angiogenesis is treated thereby. - View Dependent Claims (17, 18, 19, 23, 25, 27, 29, 31)
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33. A method of treating ocular angiogenesis in a subject in need thereof, comprising:
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administering to the subject a composition comprising a double stranded siRNA molecule that down regulates expression of a HIF1A 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 the HIF1A gene so that the siRNA molecule directs cleavage of the mRNA via RNA interference. - View Dependent Claims (34, 35, 36, 37, 38)
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39. A composition comprising an interfering RNA having a length of 19 to 49 nucleotides and having a nucleotide sequence corresponding to any one of SEQ ID NO:
- 3, and SEQ ID NO;
9-SEQ ID NO;
51, or a complement thereof, and a pharmaceutically acceptable carrier. - View Dependent Claims (40, 41, 42)
- 3, and SEQ ID NO;
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43. A composition comprising a double stranded siRNA molecule that down regulates expression of a HIF1A gene via RNA interference, wherein:
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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 the HIF1A gene so that the siRNA molecule directs cleavage of the mRNA via RNA interference. - View Dependent Claims (44, 45)
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Specification