As a first step to develop either new application routes, vehiclesand devices for siRNA delivery in skin and hair for dermatologicalinterventions, we first designed highly efficient StealthTM RNAtargeting human tyrosinase as prototype tools. Their efficacywas evaluated in human primary melanocytes by qPCR andWestern blotting. In addition, melanin production was quantifiedin a co-culture of melanocytes and keratinocytes. Melanogenesisinhibition was thus shown to be efficiently achieved with 3 distinctand potent StealthTM siRNA with optimum IC50 in the 10-100 pMrange. Transfected human skin melanocytes were then seededwith keratinocytes to reconstruct a pigmented epidermis accordingto SkinEthic procedure which was cultured for up to 39 daysin vitrothe reconstruction of an artificial epidermis showing a long termlasting (>30 days) inhibition of melanogenesis, in contrast withmelanocytes treated with a scrambled Stealth. By silencing tyrosinase in melanocytes, we achievedTM siRNA. Asexpected, this observation clearly identifies the lack of redunin the melanogenesis machinery to rescue the silencingof tyrosinase. Since skin pigmentation can easily be monitoredby colorimetric analysis, the use of validated Stealthagainst tyrosinase on reconstructed pigmented epidermis is aprecious tool for the evaluation of functional skin delivery vehiclesdancyTM siRNAand devices, which remains the major challenge towards theuse of RNAi for dermatological intervention (either cosmeticalortherapeutical).