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Rnai-mediated inhibition of ocular hypertension targets

A target, high intraocular pressure technology, applied in DNA/RNA fragments, recombinant DNA technology, etc., can solve the problems of short curative effect, reduced patient compliance, and final treatment.

Inactive Publication Date: 2008-03-05
ALCON INC
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  • Summary
  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

This negative side effect can lead to decreased patient compliance or the end of treatment
In addition, the efficacy of current IOP-lowering therapies is relatively short-lived, requiring repeated daily dosing and, in some cases, waning over time

Method used

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  • Rnai-mediated inhibition of ocular hypertension targets
  • Rnai-mediated inhibition of ocular hypertension targets

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0225] Interfering RNA for specific silencing of CA2 in HeLa cells

[0226] This study examined the ability of CA2-interfering RNA to knock down the expression level of endogenous CA2 in cultured Hela cells.

[0227] Transfection of HeLa cells was performed using standard in vitro concentrations of CA2 siRNA (100 nM and 1 nM) or no targeting control siRNA and DharmaFECT TM 1 Completed with transfection reagent (Dharmacon, Lafayette, CO). All siRNAs were dissolved in 1×siRNA buffer containing 20mM KCl, 6mM HEPES (pH 7.5), 0.2mM MgCl 2 of aqueous solution. 72 hours after transfection, CA2 protein expression and actin protein expression (loading control) were assessed by western blot analysis. CA2 siRNAs are double-stranded interfering RNAs specific for the following target sequences: siCA2#1 targets SEQ ID NO:721; siCA2#3 targets SEQ ID NO:15; siCA2#4 targets SEQ ID NO:720; siCA2 #5 targets SEQ ID NO:141. As shown by the western blot data in Figure 1, each of the four CA2 ...

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Abstract

RNA interference is provided for inhibition of ocular hypertension target mRNA expression for lowering elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Ocular hypertension targets include carbonic anhydrase II, IV, and XII; beta1- and beta2 adrenergic receptors; acetylcholinesterase; Na+ / K+-ATPase; and Na-K-2Cl cotransporter. Ocular hypertension is treated by administering interfering RNAs of the present invention.

Description

field of invention [0001] The present invention relates to the field of interfering RNA compositions for inhibiting the expression of intraocular pressure targets in glaucoma, especially primary open-angle glaucoma. Background of the invention [0002] Glaucoma is a heterogeneous group of optic nerve with certain clinical features. Vision loss in glaucoma is due to the selective death of retinal ganglion cells in the neural retina and is clinically diagnosed with characteristic changes in the visual field, nerve fiber layer defects, and progressive depression of the optic disc (ONH). One of the major risk factors for glaucoma development is the presence of ocular hypertension (elevated intraocular pressure, IOP). Proper intraocular pressure is necessary to maintain eye shape and provide a pressure gradient for aqueous humor flow to the avascular cornea and lens. The pathogenesis of normal tension glaucoma (NTG) may also involve IOP levels, as evidenced by patients benefiti...

Claims

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Application Information

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IPC IPC(8): C12N15/11A61K31/713
Inventor A·R·谢帕德J·E·查特尔顿A·F·克拉克M·B·瓦克斯
Owner ALCON INC
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