Lumasiran (ALN-G01) is a small interfering RNA therapeutic that targets hepatic glycolate oxidase mRNA, silences enzyme expression, reduces oxalate biosynthesis. Lumasiran addresses the pathogenic metabolic defect underlying primary hyperoxaluria type 1, supporting its use in translational and mechanistic disease research.

Lumasiran effectively decreased the excretion of urinary oxalate, which is responsible for the progression of kidney failure in patients with Primary Hyperoxaluria Type 1 (PH1)[1].

In vivo, Lumasiran is formulated with an N-acetylgalactosamine (GalNAc) conjugate to facilitate targeted delivery to the liver via the Asialoglycoprotein Receptor (ASGPR). In animal models of PH1 (such as Agxt-deficient mice), subcutaneous administration of the substance leads to a dose-dependent reduction in hepatic HAO1 mRNA and GO enzyme activity. Preclinical observations indicate that the suppression of GO results in elevated levels of plasma glycolate, which is efficiently excreted by the kidneys without causing stone formation, while simultaneously leading to a substantial decrease in urinary and plasma oxalate levels. These findings support the approach of substrate reduction to address the metabolic defect in PH1 [1][3].

H2O: 80 mg/mL, Sonication is recommended.