Double-stranded RNA oligonucleotides which inhibit tyrosinase expression

Abstract

Novel double-stranded RNA oligonucleotides are useful for decreasing tyrosinase expression, have cosmetic and / or pharmaceutical applications, for example are useful skin depigmenting or anti-browning agents, and can be associated with cationic particles less than or equal to 1 μm in size, having a zeta potential of from 10 to 80 mV.

Description

CROSS-REFERENCE TO PRIORITY APPLICATION [0001] This application claims priority under 35 U.S.C. § 119 of FR 05 / 09658, filed Sep. 21, 2005, hereby expressly incorporated by reference and assigned to the assignee hereof. BACKGROUND OF THE INVENTION [0002] 1. Technical Field of the Invention [0003] The present invention relates to novel double-stranded RNA oligonucleotides for decreasing tyrosinase expression, to the use thereof for cosmetic and / or pharmaceutical purposes and also to the association thereof with cationic particles less than or equal to 1 μm in size, with a zeta potential ranging from 10 to 80 mV. [0004] 2. Description of Background and / or Related and / or Prior Art [0005] Tyrosinase (monophenol dihydroxylphenylalanine: oxygen oxidoreductase EC 1.14.18.1) is the essential enzyme involved in the mechanism of skin pigmentation. It catalyzes in particular the reaction for conversion of tyrosine to Dopa (dihydroxyphenylalanine) by virtue of its hydroxylase activity and the re...

AI Technical Summary

Benefits of technology

[0029] The use of dsRNA and, more particularly, of siRNA (for short interfering RNA) makes it possible to obtain an activity of specific inhibition of the synthesis of a target protein by degradation of the mRNA encoding the protein. The degradation of the target mRNA is obtained through the activation of the RISC complex (RNA Induced Silencing Complex) which has its effect through the binding of the anti-sense strand of the dsRNA to the mRNA (see Tuschl T. Chem. Biochem., 2001; 2:239-245; Nykanen A & al, Cell 2001; 107:309-321; Dorsett Y. and Tuschl T. Nat Rev Drug Discov., 2004; 3:318-329; Downward J. BMJ. 2004; 328:1245-1248; Shanker P. et al., JAMA 2005; 293:1367-1373).

Problems solved by technology

These compounds inhibit tyrosinase but most of these compounds are cytotoxic with respect to melanocytes, which could cause permanent depigmentation of the skin.

However, the use of siRNAs in vivo is known to present various difficulties.

Judge A D et al., Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA, Nat. Biotechnol., 2005; 23:457-62) and also the induction or the inhibition of the expression of genes not targeted by the siRNA (Jackson et al., Expression profiling reveals off-target gene regulation by RNAi, Nat. Biotechnol., 2003; 21:635-7), these two phenomena are highly undesirable.

In particular, it is not demonstrated whether the siRNAs homologous to these anti-sense RNAs are effective.

In the context of a cosmetic or therapeutic use, this regulation of non-targeted genes is not acceptable, in particular due to its unpredictable nature.

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