Transthyretin messenger RNA (TTR mRNA) (TTR mRNA)

Transthyretin (TTR) messenger RNA is the genetic transcript derived from the TTR gene, primarily synthesized in the liver, which provides the template for the production of the transthyretin protein (UniProt, 2024). In both hereditary and wild-type forms of transthyretin-mediated amyloidosis (ATTR), the resulting TTR protein misfolds and accumulates as amyloid deposits in peripheral nerves and the myocardium, leading to progressive organ dysfunction (NIH, 2023). Therapeutics targeting TTR mRNA represent a significant advancement in treating these conditions by utilizing gene silencing technologies. Specifically, small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) bind to the mRNA sequence, triggering its enzymatic degradation and thereby preventing the translation of the toxic protein (PubMed, 2021). Currently approved therapies such as patisiran, vutrisiran, inotersen, and eplontersen have demonstrated efficacy in reducing serum TTR levels and slowing the progression of neuropathy and cardiomyopathy in affected patients (FDA, 2023). However, because TTR is essential for the transport of vitamin A, patients receiving these mRNA-targeted therapies must be monitored for vitamin A deficiency and typically require daily supplementation.

Other names

TTR transcriptPrealbumin mRNAPALB mRNATBPA mRNATransthyretin-encoded mRNA

Degradation of the TTR mRNA transcript through RNA interference (RNAi) or antisense oligonucleotide-mediated RNase H cleavage, which prevents the translation of the transthyretin protein (FDA, 2018; PubMed, 2021).