Determination of Complement C3 in human serum to support an investigational RNAi therapeutic

CBF 2.0 2025 -- Dysregulated activation of the complement cascade mediates tissue injury in complement-mediated kidney diseases. Complement component C3 (C3), a vital player in both innate and adaptive immunity, plays a significant role in initiating inflammatory and protective responses against pathogen challenges. The central role of C3 in the cascade makes it a unique therapeutic target for complement inhibition. The investigational RNAi therapeutic is a small interfering RNA (siRNA) designed to achieve potent and durable inhibition of complement activity by suppressing hepatic synthesis of C3. To support its clinical development, we established a quantitative assay to measure C3 concentrations in human serum based on the commercial kit, ensured parallelism and sensitivity suitable for clinical sample analysis. The optimized method demonstrated robust performance, reliably detecting >95% reduction in C3 levels following treatment.