Transcriptome sequencing data of mouse back skin injected with AAV-GPN-Rspo1

Through comprehensive in vitro and in vivo screening of AAV-delivered constructs, we identified a novel 228-bp dermis-specific promoter Gpnmb (GPN). The GPN promoter demonstrated both robust transcriptional activity and exceptional tissue specificity. Remarkably, due to evolutionary conservation, the human GPN ortholog maintained comparable performance in murine models. Intradermal administration of AAV-GPN-Rspo1 induced potent hair regrowth during resting phase in mice, while significantly reducing hepatic and subcutaneous off-target expression compared to CAG-Rspo1 controls. RNA sequencing analysis revealed that Rspo1 overexpression stimulates hair follicle activation through synergistic upregulation of Wnt and Hedgehog signaling pathways. Our findings establish the GPN promoter as a robust tool for dermis-targeted gene therapy. The AAV-GPN-Rspo1 system offers a safe and effective long-term therapeutic strategy for the treatment of hair loss.