MITF-siRNA formulation is a safe and effective therapy for human melasma.
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.
Center for Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Xiang
X
Yi
Guang
G
Zhao
Hongjie
H
Zhang
Di
D
Guan
Rusong
R
Meng
Yingyu
Y
Zhang
Qingqi
Q
Yang
Henming
H
Jia
Kejun
K
Dou
Chui
C
Liu
Fangyuan
F
Que
James Q
JQ
Yin
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008850:Microphthalmos / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D034741:RNA, Small Interfering