MITF-siRNA Formulation Is a Safe and Effective Therapy for Human Melasma

作者：Yi Xiang, Guang Zhao, Hongjie Zhang, Di Guan, Rusong Meng, Yingyu Zhang, Qingqi Yang, Henming Jia, Kejun Dou, Chui Liu, Fangyuan Que, James Q. Yin · 发表于：Molecular Therapy · 年份：2010 · DOI：10.1038/mt.2010.263 · 被引用次数：69 · 研究领域：Silk-based biomaterials and applications、RNA Interference and Gene Delivery、melanin and skin pigmentation

It is unclear whether siRNA-based agents can be a safe and effective therapy for diseases. In this study, we demonstrate that microphthalmia-associated transcription factor-siRNA (MITF-siR)-silenced MITF gene expression effectively induced a significant reduction in tyrosinase (TYR), tyrosinase-related protein 1, and melanocortin 1 receptor (MC1R) levels. The siRNAs caused obvious inhibition of melanin synthesis and melanoma cell apoptosis. Using a novel type of transdermal peptide, we developed the formulation of an MITF-siR cream. Results demonstrated that hyperpigmented facial lesions of siRNA-treated subjects were significantly lighter after 12 weeks of therapy than before treatment (P < 0.001); overall improvement was first noted after 4 weeks of siRNA treatment. At the end of treatment, clinical and colorimetric evaluations demonstrated a 90.4% lightening of the siRNA-treated lesions toward normal skin color. The relative melanin contents in the lesions and adjacent normal skin were decreased by 26% and 7.4%, respectively, after treatment with the MITF-siR formulation. Topical application of siRNA formulation significantly lightens brown facial hypermelanosis and lightens normal skin in Asian individuals. This treatment represents a safe and effective therapy for melasma, suggesting that siRNA-based agents could be developed for treating other diseases such as melanoma.