RNAi-mediated inhibition of tumor necrosis factor alpha-related conditions

A condition, the technology of the subject, applied in the direction of DNA / RNA fragments, recombinant DNA technology, medical preparations containing active ingredients, etc., can solve the problem of not teaching the target sequence, etc.

Inactive Publication Date: 2009-06-03
ARROWHEAD RES CORP
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the publication does not teach specific ta

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  • RNAi-mediated inhibition of tumor necrosis factor alpha-related conditions
  • RNAi-mediated inhibition of tumor necrosis factor alpha-related conditions
  • RNAi-mediated inhibition of tumor necrosis factor alpha-related conditions

Examples

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Embodiment 1

[0151] Example 1 is used to specifically silence the interfering RNA of TNFR1 in GTM-3 cells

[0152] This study examined the ability of TNFR1 interfering RNA to knock down endogenous TNFR1 protein expression levels in cultured GTM-3 cells.

[0153] Use TNFR1 siRNAs, siCONTROL RISC-free-siRNA #1, or siCONTROL Non-Targeting siRNA #2 (NTC2) and Standard in vitro concentrations (0.1-10 nM) of #1 transfection reagent (Dharmacon, Lafayette, CO) accomplished transfection of GTM-3 cells (Pang, I.H. et al., 1994. Curr. Eye Res. 13:51-63). Dissolve all siRNA in 1X siRNA buffer, which is 20mM KCl, 6mM HEPES (pH7.5), 0.2mM MgCl 2 of aqueous solution. Control samples included a buffer control in which the volume of siRNA was replaced with an equal volume of IX siRNA buffer (-siRNA). Western blotting was performed using an anti-TNFR antibody (Santa Cruz Biotechnology, Santa Cruz, CA) to assess TNFRl protein expression. TNFR1 siRNA is a double-stranded interfering RNA specific for the...

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Abstract

The present invention provides a RNA interferencefor inhibition of tumor necrosis factor a (TNFa) by silencing TNFa cell surface receptor TNF receptor-1 (TNFR1) mRNA expression, or by silencing TNFa converting enzyme (TACE/ADAM17) mRNA expression. Silencing such TNFa targets, in particular, is useful for treating patients having a TNFa-related condition or at risk of developing a TNFa-related condition such as the ocular conditions dry eye, allergic conjunctivitis, or ocular inflammation, or such as dermatitis, rhinitis, or asthma, for example.

Description

[0001] related application [0002] This application claims priority to co-pending U.S. Provisional Patent Application Serial No. 60 / 801,788, entitled "RNAi-Mediated Inhibition of Tumor Necrosis Factor Alpha-Associated Conditions," filed May 19, 2006, the contents of which are expressly incorporated This article serves as a reference. field of invention [0003] The application relates to the field of interfering RNA compositions, which are used to silence tumor necrosis factor alpha (TNFα) by silencing TNFα cell surface receptor TNF receptor-1 (TNFR1) mRNA or TNFα converting enzyme (TACE / ADAM17) mRNA . Silencing such TNFα targets is useful in the treatment of patients suffering from or at risk of developing a TNFα-related condition. Background of the invention [0004] Inflammation is usually treated with standard anti-inflammatory regimens including steroids and / or non-steroidal anti-inflammatory drugs (NSAIDS). Historically, allergic conjunctivitis, ocular inflammation...

Claims

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Application Information

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IPC IPC(8): C12N15/11A61K31/713C07H21/02C12N15/113
CPCA61K31/713C12N2310/14C12N15/1137C12N15/1138A61K31/7088A61P7/10A61P11/02A61P11/06A61P17/04A61P27/02A61P27/04A61P27/06A61P27/14A61P29/00A61P43/00A61K48/00C07H21/02C07H21/04C12N2310/346C12N2310/351C12N2320/30
Inventor J·M·亚恩J·E·查特尔顿D·M·森基纳D·A·盖玛彻S·T·米勒
Owner ARROWHEAD RES CORP
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