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RNAI-mediated inhibition of ocular targets

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

Inactive Publication Date: 2009-06-03
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 targets
  • RNAI-mediated inhibition of ocular targets
  • RNAI-mediated inhibition of ocular targets

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0226] Interfering RNA for specific silencing of CA2 in HeLa cells

[0227] This study examined the ability of CA2-interfering RNA to knock down the expression level of endogenous CA2 in cultured Hela cells.

[0228] 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 (pH7.5), 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 siRNA is a double-stranded interfering RNA 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. Such as figure 1 The western blot data showed that each of the four...

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PUM

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Abstract

The present invention provides a RNA interference 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

[0001] This application is a divisional application of Chinese application 200680007300.6 (PCT / US2006 / 003515) with the filing date of February 1, 2006 and the title of the invention is "RNAi-mediated inhibition of eye targets". field of invention [0002] 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 [0003] Glaucoma is a heterogeneous group of optic nerve with certain clinical characteristics. 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 ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/713A61K48/00A61P27/06C12N15/11C12N15/52
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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