Complement system messenger RNA

Complement system target mRNA refers to the messenger RNA transcripts of proteins involved in the complement cascade, a vital part of the innate immune system. These mRNAs, most notably those encoding Complement C3, Complement C5, and Complement Factor B, are targeted by novel RNA-based therapeutics such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) (1.1.1, 1.1.4). By inducing the degradation of these specific mRNA sequences, these drugs inhibit the hepatic synthesis of complement proteins, thereby reducing their systemic concentrations and preventing pathological complement activation (1.2.1, 1.4.2). This therapeutic strategy is employed to treat a variety of complement-mediated disorders, including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and generalized myasthenia gravis (gMG) (1.2.3, 1.5.4). Unlike monoclonal antibodies that bind to circulating proteins, mRNA-targeting therapies provide a long-lasting reduction in protein production, often allowing for infrequent subcutaneous dosing (1.2.2, 1.4.4). However, the profound suppression of the complement system necessitates careful monitoring for increased susceptibility to infections, particularly from encapsulated bacteria like Neisseria meningitidis (1.3.3, 1.5.5).

Other names

Complement mRNAComplement component mRNAComplement pathway mRNAComplement C5 mRNAComplement C3 mRNAComplement Factor B mRNA

RNA interference (RNAi) or antisense oligonucleotide (ASO) mediated degradation of specific complement component mRNAs to inhibit protein synthesis in the liver.