MITF-siRNA Formulation Is a Safe and Effective Therapy for Human Melasma
| Autor: | Chui Liu, Guang Zhao, Yingyu Zhang, Qingqi Yang, Xiang Yi, James Q. Yin, Henming Jia, Kejun Dou, Rusong Meng, Hongjie Zhang, Fangyuan Que, Di Guan |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Small interfering RNA
Cell Survival Melasma Tyrosinase Pharmacology Biology Melanin Mice Cell Line Tumor Drug Discovery Genetics medicine Animals Humans Microphthalmos RNA Small Interfering Melanoma Molecular Biology Transdermal Melanins Mice Inbred BALB C Microphthalmia-Associated Transcription Factor integumentary system Reverse Transcriptase Polymerase Chain Reaction Flow Cytometry Microphthalmia-associated transcription factor medicine.disease Immunology Molecular Medicine Original Article Melanocortin 1 receptor |
| Zdroj: | Molecular Therapy. 19:362-371 |
| ISSN: | 1525-0016 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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