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Rnai-mediated inhibition of ocular hypertension targets

A high intraocular pressure, targeted technology, applied in the direction of DNA / RNA fragments, recombinant DNA technology, etc., can solve the problems of treatment termination, short curative effect, weakened drug effect, etc.

Inactive Publication Date: 2008-04-02
ALCON INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This negative side effect may result in decreased patient compliance or discontinuation 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 used to specifically silence CA2 in HeLa cells

[0226] This study tested the ability of CA2-interfering RNA to knock out endogenous CA2 expression levels in cultured Hela cells.

[0227] The transfection of HeLa cells uses standard in vitro concentrations of CA2siRNA (100nM and 1nM) or no targeting control siRNA and DharmaFECT TM 1 Transfection reagent (Dharmacon, Lafayette, CO) is completed. All siRNA are dissolved in 1×siRNA buffer, which contains 20mM KCl, 6mM HEPES (pH 7.5), 0.2mM MgCl 2 Aqueous solution. 72 hours after transfection, CA2 protein expression and actin protein expression were evaluated by western blot analysis (loading control). CA2siRNA is a double-stranded interfering RNA, which has specificity 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 Targeting SEQ ID NO:141. The western blot data shown in Figure 1 shows that, relative to the non-targeting ...

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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

Invention field [0001] The present invention relates to the field of interference RNA compositions, which are used to inhibit 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 neuropathy with certain clinical characteristics. The loss of vision in glaucoma is caused by the selective death of retinal ganglion cells in the neural retina. The clinical diagnosis is characterized by characteristic changes in the visual field, nerve fiber layer defects and progressive depression of the optic disc (ONH). One of the main risk factors for the formation of glaucoma is the presence of high intraocular pressure (elevated intraocular pressure, IOP). Proper intraocular pressure is necessary to maintain the shape of the eye and provide a pressure gradient for the flow of aqueous humor to the avascular cornea and lens. The pathogenesis of common intraocular tension gl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/11A61K31/713
Inventor A·R·谢帕德J·E·查特尔顿A·F·克拉克
Owner ALCON INC
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