Flavin-containing monooxygenase 3 messenger RNA (FMO3 mRNA)

Flavin-containing monooxygenase 3 (FMO3) mRNA is the transcript encoding the major hepatic enzyme responsible for converting gut-microbiota-derived trimethylamine (TMA) into trimethylamine N-oxide (TMAO) [1, 2]. TMAO is a bioactive metabolite strongly associated with the pathogenesis of cardiovascular diseases, including atherosclerosis and thrombosis, by promoting cholesterol accumulation in macrophages and enhancing platelet hyperreactivity [2, 3]. Elevated TMAO levels are also linked to the progression of chronic kidney disease and metabolic syndrome [4]. Therapeutic targeting of FMO3 mRNA using antisense oligonucleotides (ASOs) or RNA interference (RNAi) aims to reduce FMO3 protein expression, thereby lowering systemic TMAO concentrations and reducing cardiovascular risk [3, 5]. A significant clinical challenge associated with FMO3 inhibition is the potential development of trimethylaminuria (fish odor syndrome), caused by the accumulation of unoxidized TMA excreted in sweat and breath [1, 5]. Current research focuses on optimizing the therapeutic window to lower TMAO effectively while avoiding the social and psychological burden of malodor [5].

Other names

FMO3 transcriptDimethylaniline monooxygenase [N-oxide-forming] 3 mRNAFlavin-containing dimethylaniline monooxygenase 3 mRNA

Antisense oligonucleotide-mediated degradation of FMO3 mRNA to reduce hepatic FMO3 enzyme levels and subsequent trimethylamine N-oxide (TMAO) production [3, 5].