Therapeutic Evaluation of a C3-Targeting Small Nucleic Acid Drug in a Spontaneous Humanized C3 Glomerulopathy Mouse Model

Complement component C3 is central to activation of the alternative complement pathway, and its dysregulation drives C3 glomerulopathy (C3G), a severe renal autoimmune disease lacking effective treatments. GemPharmatech established a humanized C3G mouse model (B6-hC3 mC3 KO) that overexpresses human C3 while lacking murine C3, spontaneously developing progressive glomerulopathy that recapitulates human C3G pathology. In this model, small nucleic acid drug treatment reduced serum C3 and C3a levels, suppressed alternative pathway hyperactivation, and decreased renal C3 deposition and inflammation, supporting its utility for mechanistic studies and preclinical evaluation of complement-targeted therapies.