Over the last few years, US Food and Drug Administration-approved drugs using RNA interference have come to the market. Many have treated liver-specific diseases utilizing N-acetyl galactosamine conjugation because of its effective delivery and limited off-target effects. The autosomal recessive disorder primary hyperoxaluria, specifically type 1, has benefited from these developments. Primary hyperoxaluria arises from mutations in the enzymes involved in endogenous oxalate synthesis. The severity of disease varies but can result in kidney failure and systemic oxalosis. Until recently, the treatment options were limited and focused primarily on supportive treatments, pyridoxine use in a subset of patients with primary hyperoxaluria type 1, and liver-kidney transplants in those who progressed to kidney failure. Two genes have been targeted with RNA interference; lumasiran targets glycolate oxidase and nedosiran targets lactate dehydrogenase A. Lumasiran was recently approved in the treatment of primary hyperoxaluria type 1 and nedosiran is in the approval process. Unfortunately, despite initial hopes that nedosiran may also be a treatment option for primary hyperoxaluria types 2 and 3, initial data suggest otherwise. The use of RNA interference liver-specific targeting for the treatment of primary hyperoxaluria type 1 will likely transform the natural history of the disease.

在过去的几年里，美国食品和药物管理局批准的使用 RNA 干扰的药物已经上市。许多人利用N治疗肝脏特异性疾病-乙酰半乳糖胺缀合，因为它的有效递送和有限的脱靶效应。常染色体隐性遗传病原发性高草酸尿症，特别是 1 型，已从这些发展中受益。原发性高草酸尿症源于参与内源性草酸合成的酶的突变。疾病的严重程度各不相同，但可导致肾衰竭和全身性草酸中毒。直到最近，治疗选择还很有限，主要集中在支持性治疗、吡哆醇用于部分原发性高草酸尿症 1 型患者以及进展为肾功能衰竭的患者中的肝肾移植。两个基因已被 RNA 干扰靶向；lumasiran 靶向乙醇酸氧化酶，nedosiran 靶向乳酸脱氢酶 A。Lumasiran 最近被批准用于治疗 1 型原发性高草酸尿症，而 nedosiran 正在审批过程中。不幸的是，尽管最初希望 nedosiran 也可能是 2 型和 3 型原发性高草酸尿症的一种治疗选择，但最初的数据表明并非如此。使用 RNA 干扰肝脏特异性靶向治疗 1 型原发性高草酸尿症可能会改变该疾病的自然史。