Efficacy of Asymmetric siRNA Targeting Androgen Receptors for the Treatment of Androgenetic Alopecia

The study investigated the use of asymmetric small interfering RNAs (asiRNAs) targeting androgen receptors (AR) for treating androgenetic alopecia (AGA). Researchers developed AGA mouse models and used ex vivo human scalp tissues to evaluate the efficacy of a cell-penetrating, AR-targeting asiRNA (cp-asiAR). The cp-asiAR was designed to silence the AR gene, reducing mRNA and protein levels of AR, and promoting hair growth in mouse models with DHT-induced AGA. In human hair follicle cultures, cp-asiAR treatment decreased the proportion of telogen hair and increased hair bulb diameter. Additionally, cp-asiAR effectively downregulated AR expression in primary human dermal papilla cells and attenuated DHT-mediated increases in interleukin-6, transforming growth factor-β1, and dickkopf-1 levels, without significant toxicity. These findings suggest cp-asiAR as a promising therapeutic option for AGA.