RNAI-mediated inhibition of tumor necrosis factor α-related conditions
AssigneeAlcon Research, Ltd.
InventorsJohn M. Yanni, Jon E. Chatterton, Diane Michelle Senchyna, Daniel A. Gamache, Steven T. Miller
Life of this patent
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Abstract
RNA interference is provided for inhibition of tumor necrosis factor α (TNFα) by silencing TNFα cell surface receptor TNF receptor-1 (TNFR1) mRNA expression, or by silencing TNFα converting enzyme (TACE/ADAM17) mRNA expression. Silencing such TNFα targets, in particular, is useful for treating patients having a TNFα-related condition or at risk of developing a TNFα-related condition such as the ocular conditions dry eye, allergic conjunctivitis, or ocular inflammation, or such as dermatitis, rhinitis, or asthma, for example.
Claims12
A method of attenuating expression of TNFR1 mRNA of 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, an antisense nucleotide strand, and the sense and antisense strands comprise a region of 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:2 beginning at nucleotide 1324;
- wherein the expression of TNFR1 mRNA is attenuated thereby.
A method of treating a TNFα-related ocular condition in a subject in need thereof, 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, an antisense nucleotide strand, and the sense and antisense strands comprise a region of 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:2 beginning at nucleotide 1324;
- wherein the TNFα-related ocular condition is treated thereby, and wherein the TNFα-related ocular condition is dry eye, allergic conjunctivitis or ocular inflammation.
Dependencies are inferred from the claim text.