Lumasiran是一种靶向羟基酸氧化酶1（HAO1）mRNA的特异性siRNA治疗药物。
Cas No.:1834610-13-7
Sample solution is provided at 25 µL, 10mM.
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Lumasiran is a specific siRNA therapeutic targeting hydroxyacid oxidase 1 (HAO1) mRNA[1]. Covalently conjugated with N-acetylgalactosamine (GalNAc), Lumasiran specifically silences HAO1 gene expression through an RNA interference mechanism, blocking the translation of glycolate oxidase (GO)[2]. GO is a hepatic peroxisomal enzyme that catalyzes the oxidation of glycolate to glyoxylate, the immediate precursor for oxalate synthesis in hepatocytes[3]. Lumasiran has liver targeting and achieves specific delivery by binding to the highly expressed assialoglycoprotein receptor (ASGPR) in hepatocytes[4]. Lumasiran is usually used in the study of primary hyperoxaluria type 1 (PH1)[5][6].
In vivo, Lumasiran (3mg/kg/week; subcutaneous injections for 4 weeks) resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and reduced urinary oxalate concentration by 98% in rats with hyperoxaluria induced by AGXT knockdown and ethylene glycol feeding[7].
References:
[1] Scott LJ, Keam SJ. Lumasiran: First Approval. Drugs. 2021;81(2):277-282.
[2] Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1. N Engl J Med. 2021;384(13):1216-1226.
[3] Hoppe B, Martin-Higueras C. Improving Treatment Options for Primary Hyperoxaluria. Drugs. 2022;82(10):1077-1094.
[4] D'Ambrosio V, Ferraro PM. Lumasiran in the Management of Patients with Primary Hyperoxaluria Type 1: From Bench to Bedside. Int J Nephrol Renovasc Dis. 2022;15:197-206.
[5] Gang X, Liu F, Mao J. Lumasiran for primary hyperoxaluria type 1: What we have learned?. Front Pediatr. 2023;10:1052625.
[6] Hulton SA, Groothoff JW, Frishberg Y, et al. Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1. Kidney Int Rep. 2021;7(3):494-506.
[7] Liebow A, Li X, Racie T, et al. An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria. J Am Soc Nephrol. 2017;28(2):494-503.
Lumasiran是一种靶向羟基酸氧化酶1（HAO1）mRNA的特异性siRNA治疗药物[1]。Lumasiran与N-乙酰半乳糖胺（GalNAc）共价偶联，通过RNA干扰机制特异性沉默HAO1基因表达，阻断乙醇酸氧化酶（GO）的翻译过程[2]。GO是一种肝脏过氧化物酶，催化乙醇酸氧化为乙醛酸盐，是肝细胞中草酸盐合成的直接前体[3]。Lumasiran具有肝脏靶向性，通过与肝细胞高表达的去唾液酸糖蛋白受体（ASGPR）结合实现特异性递送[4]。Lumasiran通常用于原发性高草酸尿症1型（PH1）的研究[5][6]。
体内实验中，在AGXT敲低和乙二醇喂养引起的高草酸尿大鼠中，Lumasiran（3mg/kg/周；皮下注射；4周）导致编码乙醇酸氧化酶的mRNA有效、剂量依赖性和持久的沉默，并使尿草酸浓度降低98%[7]。
| Animal experiment [1]: | |
Animal models | Male Sprague-Dawley rats |
Preparation Method | Male Sprague-Dawley rats weighing approximately 150g upon arrival were used to create an induced rat model of hyperoxaluria. Rats were housed continuously in metabolic cages and received weekly intravenous doses of 1mg/kg AGXT targeting siRNA formulated in an LNP to reduce AGXT levels to more closely resemble the PH1 disease state. Rats received subcutaneous injections of PBS or Lumasiran (3mg/kg/week) for 4 weeks. Urinary oxalate increases were further induced with ethylene glycol provided as 1% v/v in the drinking water daily. Twenty-four-hour urinary oxalate levels were evaluated at multiple time points and liver mRNA levels were evaluated by quantitative PCR in animals euthanized on day 14 or 28. |
Dosage form | 3mg/kg/week; subcutaneous injections for 4 weeks |
Applications | Lumasiran resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and reduced urinary oxalate concentration by 98% in rats with hyperoxaluria induced by AGXT knockdown and ethylene glycol feeding. |
References: | |
| Cas No. | 1834610-13-7 | SDF | Download SDF |
| 别名 | ALN-G01 | ||
| 分子式 | C530H712F10N173O320P43S6 | 分子量 | 16339.00 (AS: 7631.0 +SS: 8708.0) |
| 溶解度 | 储存条件 | Store at -20°C | |
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1 mg | 5 mg | 10 mg |
| 1 mM | 61.2 μL | 306 μL | 612 μL |
| 5 mM | 12.2 μL | 61.2 μL | 122.4 μL |
| 10 mM | 6.1 μL | 30.6 μL | 61.2 μL |
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每只动物给药体积 | ul | |
动物数量 | 只 |
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2.
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