Transthyretin mRNA, 3′ untranslated region (TTR mRNA 3' UTR) (TTR mRNA 3' UTR)

Transthyretin (TTR) mRNA, specifically its 3′ untranslated region (3′ UTR), is a validated therapeutic target for the treatment of transthyretin-mediated amyloidosis (ATTR) [PMID: 30044866]. TTR is a transport protein produced primarily in the liver that carries thyroxine and retinol-binding protein-bound vitamin A in the blood [UniProt: P02766]. In patients with ATTR, the TTR protein misfolds and aggregates into amyloid fibrils that deposit in various organs, most notably the peripheral nerves and the heart, leading to progressive polyneuropathy and cardiomyopathy [PMID: 31235047]. Therapeutic strategies targeting the 3′ UTR of TTR mRNA utilize small interfering RNAs (siRNAs) or antisense oligonucleotides (ASOs) to reduce the production of both mutant and wild-type TTR protein [FDA Label: Onpattro, Tegsedi]. These drugs bind to the 3′ UTR and trigger the degradation of the mRNA transcript through the RNA-induced silencing complex (RISC) or RNase H-mediated cleavage [PMID: 29972753]. By lowering the concentration of circulating TTR protein, these therapies aim to prevent further amyloid deposition and stabilize or improve organ function in affected patients [PMID: 35744322].

Other names

TTR mRNA 3' UTRTransthyretin 3' untranslated regionTTR 3' UTRTransthyretin messenger RNA 3' UTR

RNA interference (RNAi) and antisense oligonucleotide (ASO) mediated degradation of mRNA transcripts to inhibit protein translation [PMID: 29972753, PMID: 30044866].