A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) mRNA (ADAMTS13 mRNA)

ADAMTS13 mRNA encodes the zinc-metalloprotease responsible for cleaving ultra-large von Willebrand factor (UL-VWF) multimers into smaller, less prothrombotic fragments (UniProt P59510). In the absence of functional ADAMTS13, these large multimers accumulate, leading to spontaneous platelet aggregation and the life-threatening condition known as thrombotic thrombocytopenic purpura (TTP) (NIH StatPearls). While traditional treatments involve plasma exchange or recombinant protein replacement, mRNA-based therapies aim to deliver the genetic instructions for ADAMTS13 directly to the patient's cells, typically the liver, to facilitate endogenous production of the enzyme (Moderna Pipeline). This approach, exemplified by candidates like mRNA-3902, offers a potential long-term solution for congenital TTP (Upshaw-Schulman syndrome) by maintaining steady-state levels of the protease (PubMed PMC8143087). Current clinical development focuses on utilizing lipid nanoparticle delivery systems to ensure efficient translation and secretion of the functional protein into the bloodstream while monitoring for potential immunogenic responses to the mRNA or delivery vehicle (Journal of Thrombosis and Haemostasis).

Other names

von Willebrand factor-cleaving protease mRNAVWFCP mRNAADAM-TS13 mRNAC9orf8 mRNA

mRNA-mediated endogenous protein expression