mRNA-3928

mRNA-3928 is an investigational, lipid nanoparticle (LNP)-encapsulated mRNA therapy developed by Moderna for the treatment of methylmalonic acidemia (MMA), specifically isolated methylmalonyl-CoA mutase (MUT) deficiency. The drug consists of a modified messenger RNA sequence that encodes a functional human MUT enzyme, incorporating a specific polymorphism at position 671 (H671R). This polymorphism is a common natural variant that maintains enzymatic activity. Upon intravenous administration, the LNPs facilitate the delivery of the mRNA to hepatocytes. Once inside the cells, the mRNA is translated into the MUT protein, which then translocates to the mitochondria. There, it restores the enzymatic conversion of methylmalonyl-CoA to succinyl-CoA, thereby reducing the systemic accumulation of toxic metabolites such as methylmalonic acid. mRNA-3928 is currently being evaluated in the Phase 1/2 Paramount clinical trial as a potential long-term treatment to prevent metabolic crises and improve clinical outcomes in patients with MMA.

Other names

modified messenger RNA encoding human methylmalonyl-coenzyme A mutase containing a polymorphism at position 671