Recent Application of Intronic MicroRNA Agents in Cosmetics

Abstract Utilization of gene silencing effectors, such as microRNA (miRNA) and small hairpin RNA (shRNA), provides a powerful new strategy for human skin care in vivo, particularly for hyperpigmentation treatment and aging prevention. For example, tyrosinase (Tyr), a melanocytic membrane-bound glycoprotein, is the rate-limiting enzyme critical for melanin (black pigment) biosynthesis in skins and hairs. There are over 54 native microRNA capable of targeting human tyrosinase for skin whitening and lightening. In this study, we have designed a mir-434-5p homologue and used it to successfully demonstrate the feasibility of miRNA-mediated skin whitening in vitro and in vivo. Under the same experimental condition in trials, Pol-II-directed intronic mir-434-5p expression did not cause any detectable sign of cytotoxicity, whereas siRNAs targeting the same sequence induced certain non-specific mRNA degradation as previously reported. Because the intronic miRNA-mediated gene silencing pathway is tightly regulated by multiple intracellular surveillance systems, including Pol-II transcription, RNA splicing, exosome digestion and NMD processing, the current findings underscore the fact that intronic miRNA agents, such as mir-434-5p homologues, are effective, target-specific and safe to be used for skin whitening without any overt cytotoxic effect. Given that the human skins also express a variety of native miRNAs, we may re-design these miRNAs based on their individual functions for skin care, which will provide significant insights into areas of opportunity for new cosmetic interventions.