Targeted siRNA Therapy for Psoriasis: Translating Preclinical Potential into Clinical Treatments

Fuyu Zhao,1– 3,* Jianan Zhao,1– 3,* Kai Wei,1– 3 Ping Jiang,1– 3 Yiming Shi,1– 3 Cen Chang,1– 3 Yixin Zheng,1– 3 Yu Shan,1– 3 Yunshen Li,1– 3 Bingheng He,4 Mi Zhou,1,3 Jia Liu,1,3 Li Li,1,3 Shicheng Guo,1 Dongyi He1– 3 1Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Rehabilitation, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongyi He, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email dongyihe@medmail.com.cnAbstract: Psoriasis is a chronic inflammatory skin disease characterized by the excessive proliferation of keratinocytes and heightened immune activation. Targeting pathogenic genes through small interfering RNA (siRNA) therapy represents a promising strategy for the treatment of psoriasis. This mini-review provides a comprehensive summary of siRNA research targeting the pathogenesis of psoriasis, covering aspects such as keratinocyte function, inflammatory cell roles, preclinical animal studies, and siRNA delivery mechanisms. It details recent advancements in RNA interference that modulate key factors including keratinocyte proliferation (Fibroblast Growth Factor Receptor 2, FGFR2), apoptosis (Interferon Alpha Inducible Protein 6, G1P3), differentiation (Grainyhead Like Transcription Factor 2, GRHL2), and angiogenesis (Vascular Endothelial Growth Factor, VEGF); immune cell infiltration and inflammation (Tumor Necrosis Factor-Alpha, TNF-α; Interleukin-17, IL-17); and signaling pathways (JAK-STAT, Nuclear Factor Kappa B, NF-κB) that govern immunopathology. Despite significant advances in siRNA-targeted treatments for psoriasis, several challenges persist. Continued scientific developments promise the creation of more effective and safer siRNA medications, potentially enhancing the quality of life for psoriasis patients and revolutionizing treatments for other diseases. This article focuses on the most recent research advancements in targeting the pathogenesis of psoriasis with siRNA and explores its future therapeutic prospects.Keywords: psoriasis, siRNA, keratinocytes, targeted delivery