Complement component 5 mRNA (C5 mRNA)

Complement component 5 (C5) mRNA is the genetic template for the C5 protein, a central component of the complement system's terminal pathway (UniProt P01031). The C5 protein is primarily synthesized in the liver and, once activated, is cleaved into C5a, a potent pro-inflammatory anaphylatoxin, and C5b, which initiates the assembly of the membrane attack complex (MAC) responsible for cell lysis (PubMed: 28814740). Pathological overactivation of this pathway is a key driver in diseases such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), where it causes uncontrolled intravascular hemolysis and thrombotic microangiopathy (NIH: StatPearls). By targeting the C5 mRNA with RNA interference (RNAi) therapeutics like cemdisiran, the production of C5 protein can be significantly suppressed at its source in the liver (Alnylam Pharmaceuticals). This therapeutic approach aims to provide sustained inhibition of the complement cascade, potentially offering more consistent drug levels and reduced dosing frequency compared to protein-targeting monoclonal antibodies. However, like all terminal complement inhibitors, reducing C5 levels increases the risk of life-threatening infections by encapsulated bacteria, particularly Neisseria meningitidis (FDA: Soliris/Ultomiris labels).

Other names

C5CPAMD4Complement C5Complement C5 mRNA

RNA interference (RNAi) mediated degradation of C5 mRNA in hepatocytes to inhibit the synthesis and systemic secretion of C5 protein.