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Fibrinogen alpha chain mRNA is the messenger RNA transcript of the FGA gene, which encodes the alpha subunit of fibrinogen, a 340 kDa hexameric glycoprotein essential for blood coagulation (UniProt: P02671). Fibrinogen is synthesized in the liver and converted into fibrin by thrombin during the final stage of the coagulation cascade to form a stable blood clot (PubMed: 30243534). Mutations in the C-terminal region of the FGA gene lead to hereditary fibrinogen A alpha-chain amyloidosis, a rare autosomal dominant condition where misfolded alpha-chain fragments aggregate into amyloid fibrils, primarily depositing in the renal glomeruli and leading to end-stage renal disease (NIH: Genetic and Rare Diseases Information Center). Therapeutic targeting of FGA mRNA using antisense oligonucleotides (ASOs), such as IONIS-FGA-LRx (also known as AKCEA-FGA-LRx), utilizes RNase H1-mediated degradation to reduce the hepatic production of the fibrinogen alpha chain (ClinicalTrials.gov: NCT05158309). By lowering the circulating levels of the amyloidogenic precursor protein, these therapies aim to halt or reverse amyloid deposition and preserve organ function, though they necessitate careful monitoring of plasma fibrinogen levels to mitigate the risk of bleeding (PubMed: 34161488).
Antisense oligonucleotide-mediated degradation of mRNA via RNase H1, leading to reduced translation of the fibrinogen alpha chain protein.
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