Screening and Optimization of BMP2-Targeting siRNAs for Acceleration of Telogen-Anagen Transition and Hair Regrowth

Alopecia is a common disorder characterized by dysregulation of the hair follicle (HF) growth cycle, particularly the impaired activation of telogen follicles into a new anagen stage. Bone morphogenetic protein 2 (BMP2) acts as a critical inhibitory regulator that maintains hair follicle quiescence during early telogen, and its downregulation is closely associated with the telogen-to-anagen transition. Here, we designed and screened a series of siRNAs specifically targeting BMP2 and identified a human-mouse homologous siRNA candidate siBMP2-13. The chemically modified candidate (siBMP2-13-C) exhibited strong gene-silencing activity in HSF cells (IC₅₀ = 0.20 nM). In early telogen mice, intradermal administration of the cholesterol-conjugated candidate (Chol-siBMP2-13-C) effectively reduced BMP2 expression in skin tissues, activated hair follicle stem cells, accelerated anagen onset, and enhanced hair regrowth. These findings support BMP2-targeting siRNA as a promising RNA interference-based strategy for the telogen to anagen transition and hair regrowth.