ALC-0315
目录号 : GC19792
ALC-0315 是 COVID-19mRNA 疫苗的关键成分，也是核酸治疗研究中备受追捧的脂质。
Cas No.:2036272-55-4
Sample solution is provided at 25 µL, 10mM.
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ALC-0315 is a key component of the COVID‐19mRNA vaccine and a highly sought-after lipid for nucleic acid therapeutics research [1]. Ionizable cationic lipids are essential for efficient in vivo delivery of RNA by lipid nanoparticles (LNPs). DLin-MC3-DMA (MC3), ALC-0315, and SM-102 are the only ionizable cationic lipids currently clinically approved for RNA therapies. ALC-0315 and SM-102 are structurally similar lipids used in SARS-CoV-2 mRNA vaccines [2].
Cationic lipids (CLs) and ionizable lipids (ILs) initiate the first step of self-assembly via electrostatic interactions. because of toxicity issues and lack of in vivo efficacy, CLs have been replaced by pH-sensitive ILs. The overall architecture of CLs and ILs can be broken down into three parts: (1) the headgroup, (2) the linker, and (3) the tails. The headgroups of ALC-0315 contain a terminal hydroxyl group which could decrease the hydration of the headgroup and improve hydrogen-bonding interactions with the nucleic acid, potentially leading to improved transfection ability. The linker typically connects the headgroup with the tails, although the linkers may also be buried within the tails. DLin-MC3-DMA, ALC-0315, and SM-102 all have ester linkers. DLin-MC3-DMA has two linoleyl tails, while ALC-0315 and SM-102 contain two branched saturated tails that are postulated to endow a cone-shaped geometry, facilitating destabilization of the endosomal membrane and cytosolic release of the nucleic acid [3].
References:
[1]. Saadati F, Cammarone S, Ciufolini M A. A Route to Lipid ALC‐0315: a Key Component of a COVID‐19 mRNA Vaccine[J]. Chemistry–A European Journal, 2022, 28(48): e202200906.
[2]. Ferraresso F, Strilchuk A W, Juang L J, et al. Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells[J]. Molecular Pharmaceutics, 2022.
[3]. Eygeris Y, Gupta M, Kim J, et al. Chemistry of lipid nanoparticles for RNA delivery[J]. Accounts of Chemical Research, 2021, 55(1): 2-12.
ALC-0315 是 COVID-19mRNA 疫苗的关键成分，也是核酸治疗研究中备受追捧的脂质[1]。可电离的阳离子脂质对于通过脂质纳米粒子 (LNP) 在体内有效递送 RNA 至关重要。 DLin-MC3-DMA (MC3)、ALC-0315 和 SM-102 是目前临床上唯一批准用于 RNA 疗法的可电离阳离子脂质。 ALC-0315 和 SM-102 是结构相似的脂质，用于 SARS-CoV-2 mRNA 疫苗[2]。
阳离子脂质 (CL) 和可电离脂质 (IL) 通过静电相互作用启动自组装的第一步。由于毒性问题和缺乏体内功效，CL 已被 pH 敏感的 IL 取代。 CL 和 IL 的整体架构可以分为三个部分:(1) headgroup，(2) linker，和 (3) tails。 ALC-0315 的头部含有一个末端羟基，可以减少头部的水合作用并改善与核酸的氢键相互作用，从而可能提高转染能力。接头通常将头部与尾部连接起来，尽管接头也可以埋在尾部内。 DLin-MC3-DMA、ALC-0315 和 SM-102 都具有酯接头。 DLin-MC3-DMA 有两个亚油基尾巴，而 ALC-0315 和 SM-102 包含两个分支的饱和尾巴，假定它们具有锥形几何形状，促进内体膜的去稳定化和核酸的胞质释放 [3].
| siRNA–LNP Formulation and Analysis [1]: | |
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Preparation Method |
siRNAs were dissolved in sodium acetate (pH 4) and combined with a lipid solution at an amine-to-phosphate (N/P) ratio of 3. The lipid formulations consisted of DSPC, cholesterol, and PEG-DMG at a 10:38.5:1.5% molar ratio, with either 50% DLin-MC3-DMA or ALC-0315. The LNPs were dialyzed against phosphate-buffered saline (PBS) at pH 7.4 in 500-fold excess. For quality control, cholesterol content was measured using the Cholesterol E Assay Kit. To determine siRNA concentration and entrapment, a RiboGreen assay was used. Encapsulation efficiency was measured by comparing Ribogreen signal in LNP samples with or without Triton X-100 detergent. Particle size was measured using a Malvern-Zetasizer Nano. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6J mice |
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Preparation Method |
2′-O-Methylated siRNA targeting murine FVII (siFVII), ADAMTS13 (siADAMTS13) and a negative control siRNA targeting luciferase (siLuc) were used. The resulting LNPs were diluted to a final concentration of 0.1 mg/mL siRNA in PBS prior to intravenous (IV) injection. Injected mice with 1 mg siRNA per kg body weight (mg/kg) for knockdown studies and 5 mg/kg dose for toxicity studies. |
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Dosage form |
1, 5 mg/kg |
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Applications |
Mice treated with siADAMTS13-ALC-0315 at the same dose had greater ADAMTS13mRNA and protein knockdown, compared to mice treated with siADAMTS13-MC3. |
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References: [1] : Ferraresso F, Strilchuk A W, Juang L J, et al. Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells[J]. Molecular Pharmaceutics, 2022. |
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| Cas No. | 2036272-55-4 | SDF | |
| Canonical SMILES | OCCCCN(CCCCCCOC(C(CCCCCC)CCCCCCCC)=O)CCCCCCOC(C(CCCCCC)CCCCCCCC)=O | ||
| 分子式 | C₄₈H₉₅NO₅ | 分子量 | 766.27 |
| 溶解度 | DMSO : 100 mg/mL (130.50 mM) Ethanol : 100 mg/mL (130.50 mM) | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.305 mL | 6.5251 mL | 13.0502 mL |
| 5 mM | 0.261 mL | 1.305 mL | 2.61 mL |
| 10 mM | 0.1305 mL | 0.6525 mL | 1.305 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet