DLinDMA
(Synonyms: 1,2-Dilinoleyloxy-N,N-dimethyl-3-aminopropane) 目录号 : GC33476DLinDMA 是以稳定的核酸脂质颗粒为基准的关键脂质成分。
Cas No.:871258-12-7
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
Cell experiment [1]: | |
Cell lines |
HEK293 cells and SK-N-SH cells |
Preparation Method |
Cells were treated with DLinDMA liposomes at concentrations ranging from 1.56 to 200 µM. Transit LT1 and PEI max were used as positive controls. |
Reaction Conditions |
DLinDMA 1.56 to 200 µM for 48h |
Applications |
Cell proliferation assay results showed that these liposomal formulations are nontoxic at lower concentrations. A significant decrease in cell proliferation was only observed at the concentrations ranging from 25 to 200 µM for DLinDMA liposomal formulations |
Animal experiment [2]: | |
Animal models |
C57BL/6 mice |
Preparation Method |
Mice received a single dose of LNP( Consisting of DLinDMA) -formulated Factor VII siRNA through bolus tail vein injection and serum was collected from animals 24 h after administration to analyze Factor VII protein level. |
Applications |
As a key lipid component of nucleic acid lipid granules (SNALP), DLinDMA can deliver small interfering RNA (siRNA) in mice. |
References: [1]. Vemana HP, Saraswat A, et,al. A novel gene therapy for neurodegenerative Lafora disease via EPM2A-loaded DLinDMA lipoplexes. Nanomedicine (Lond). 2021 Jun;16(13):1081-1095. doi: 10.2217/nnm-2020-0477. Epub 2021 May 7. PMID: 33960213; PMCID: PMC8162161. |
DLinDMA is a key lipid component of stable nucleic acid lipid particles as a benchmark. DLinDMA can be used to deliver siRNA[1].
DLinDMA liposomal formulation was nontoxic at lower concentrations. A significant decrease in cell proliferation was only observed at the highest concentration 200 µM for DOTAP and at concentrations ranging from 25 to 200 µM for DLinDMA liposomal formulations[2]. In a macrophage cell-line, LNP containing DLinKC2-DMA, DLinKDMA, or DLinDMA, which lack ester linkages, are not vulnerable to lipase digestion and facilitate much more potent gene silencing[3].
As a key lipid component of nucleic acid lipid granules (SNALP), DLinDMA can deliver small interfering RNA (siRNA) in mice[1].
References:
[1]. Semple SC, Akinc A,et,al. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol. 2010 Feb;28(2):172-6. doi: 10.1038/nbt.1602. Epub 2010 Jan 17. PMID: 20081866.
[2]. Vemana HP, Saraswat A, et,al. A novel gene therapy for neurodegenerative Lafora disease via EPM2A-loaded DLinDMA lipoplexes. Nanomedicine (Lond). 2021 Jun;16(13):1081-1095. doi: 10.2217/nnm-2020-0477. Epub 2021 May 7. PMID: 33960213; PMCID: PMC8162161.
[3]. Lin PJ, Tam YY, et,al.Influence of cationic lipid composition on uptake and intracellular processing of lipid nanoparticle formulations of siRNA. Nanomedicine. 2013 Feb;9(2):233-46. doi: 10.1016/j.nano.2012.05.019. Epub 2012 Jun 12. PMID: 22698807.
DLinDMA 是以稳定的核酸脂质颗粒为基准的关键脂质组分。 DLinDMA 可用于递送 siRNA[1]。
DLinDMA 脂质体制剂在较低浓度下无毒。仅在 DOTAP 的最高浓度 200 µM 和 DLinDMA 脂质体制剂的浓度范围为 25 至 200 µM 时观察到细胞增殖显着下降[2]。在巨噬细胞系中,含有缺乏酯键的 DLinKC2-DMA、DLinKDMA 或 DLinDMA 的 LNP 不易被脂肪酶消化,并促进更有效的基因沉默[3]。
作为核酸脂质颗粒 (SNALP) 的关键脂质成分,DLinDMA 可以在小鼠体内递送小干扰 RNA (siRNA)[1]。
Cas No. | 871258-12-7 | SDF | |
别名 | 1,2-Dilinoleyloxy-N,N-dimethyl-3-aminopropane | ||
Canonical SMILES | CCCCC/C=C\C/C=C\CCCCCCCCOCC(OCCCCCCCC/C=C\C/C=C\CCCCC)CN(C)C | ||
分子式 | C41H77NO2 | 分子量 | 616.06 |
溶解度 | Ethanol : ≥ 100 mg/mL (162.32 mM);DMSO : < 1 mg/mL (insoluble or slightly soluble) | 储存条件 | Store at -20°C |
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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.6232 mL | 8.1161 mL | 16.2322 mL |
5 mM | 0.3246 mL | 1.6232 mL | 3.2464 mL |
10 mM | 0.1623 mL | 0.8116 mL | 1.6232 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。
Rational design of cationic lipids for siRNA delivery
Nat Biotechnol 2010 Feb;28(2):172-6.PMID:20081866DOI:10.1038/nbt.1602.
We adopted a rational approach to design cationic lipids for use in formulations to deliver small interfering RNA (siRNA). Starting with the ionizable cationic lipid 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA), a key lipid component of stable nucleic acid lipid particles (SNALP) as a benchmark, we used the proposed in vivo mechanism of action of ionizable cationic lipids to guide the design of DLinDMA-based lipids with superior delivery capacity. The best-performing lipid recovered after screening (DLin-KC2-DMA) was formulated and characterized in SNALP and demonstrated to have in vivo activity at siRNA doses as low as 0.01 mg/kg in rodents and 0.1 mg/kg in nonhuman primates. To our knowledge, this represents a substantial improvement over previous reports of in vivo endogenous hepatic gene silencing.
Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids
J Control Release 2005 Oct 3;107(2):276-87.PMID:16054724DOI:10.1016/j.jconrel.2005.06.014.
An analogous series of cationic lipids (1,2-distearyloxy-N,N-dimethyl-3-aminopropane (DSDMA), 1,2-dioleyloxy-N,N-dimethyl-3-aminopropane (DODMA), 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA) and 1,2-dilinolenyloxy-N,N-dimethyl-3-aminopropane (DLenDMA)) possessing 0, 1, 2 or 3 double bonds per alkyl chain respectively, was synthesized to determine the correlation between lipid saturation, fusogenicity and efficiency of intracellular nucleic acid delivery. 31P-NMR analysis suggests that as saturation increases, from 2 to 0 double bonds, lamellar (L(alpha)) to reversed hexagonal (H(II)) phase transition temperature increases, indicating decreasing fusogenicity. This trend is largely reflected by the efficiency of gene silencing observed in vitro when the lipids are formulated as Stable Nucleic Acid Lipid Particles (SNALPs) encapsulating small inhibitory RNA (siRNA). Uptake experiments suggest that despite their lower gene silencing efficiency, the less fusogenic particles are more readily internalized by cells. Microscopic visualization of fluorescently labelled siRNA uptake was supported by quantitative data acquired using radiolabelled preparations. Since electrostatic binding is a precursor to uptake, the pKa of each cationic lipid was determined. The results support a transfection model in which endosomal release, mediated by fusion with the endosomal membrane, results in cytoplasmic translocation of the nucleic acid payload.
A novel gene therapy for neurodegenerative Lafora disease via EPM2A-loaded DLinDMA lipoplexes
Nanomedicine (Lond) 2021 Jun;16(13):1081-1095.PMID:33960213DOI:10.2217/nnm-2020-0477.
Aim: To develop novel cationic liposomes as a nonviral gene delivery vector for the treatment of rare diseases, such as Lafora disease - a neurodegenerative epilepsy. Materials & methods: DLinDMA and DOTAP liposomes were formulated and characterized for the delivery of gene encoding laforin and expression of functional protein in HEK293 and neuroblastoma cells. Results: Liposomes with cationic lipids DLinDMA and DOTAP showed good physicochemical characteristics. Nanosized DLinDMA liposomes demonstrated desired transfection efficiency, negligible hemolysis and minimal cytotoxicity. Western blotting confirmed successful expression and glucan phosphatase assay demonstrated the biological activity of laforin. Conclusion: Our study is a novel preclinical effort in formulating cationic lipoplexes containing plasmid DNA for the therapy of rare genetic diseases such as Lafora disease.
Influence of cationic lipid composition on uptake and intracellular processing of lipid nanoparticle formulations of siRNA
Nanomedicine 2013 Feb;9(2):233-46.PMID:22698807DOI:10.1016/j.nano.2012.05.019.
The in vivo gene silencing potencies of lipid nanoparticle (LNP)-siRNA systems containing the ionizable cationic lipids DLinDAP, DLinDMA, DLinKDMA, or DLinKC2-DMA can differ by three orders of magnitude. In this study, we examine the uptake and intracellular processing of LNP-siRNA systems containing these cationic lipids in a macrophage cell-line in an attempt to understand the reasons for different potencies. Although uptake of LNP is not dramatically influenced by cationic lipid composition, subsequent processing events can be strongly dependent on cationic lipid species. In particular, the low potency of LNP containing DLinDAP can be attributed to hydrolysis by endogenous lipases following uptake. LNP containing DLinKC2-DMA, DLinKDMA, or DLinDMA, which lack ester linkages, are not vulnerable to lipase digestion and facilitate much more potent gene silencing. The superior potency of DLinKC2-DMA compared with DLinKDMA or DLinDMA can be attributed to higher uptake and improved ability to stimulate siRNA release from endosomes subsequent to uptake. From the clinical editor: This study reports on the in vivo gene silencing potency of lipid nanoparticle-siRNA systems containing ionizable cationic lipids. It is concluded that the superior potency of DLinKC2-DMA compared with DLinKDMA or DLinDMA can be attributed to their higher uptake thus improved ability to stimulate siRNA release from endosome.
Influence of cationic lipid composition on gene silencing properties of lipid nanoparticle formulations of siRNA in antigen-presenting cells
Mol Ther 2011 Dec;19(12):2186-200.PMID:21971424DOI:10.1038/mt.2011.190.
Lipid nanoparticles (LNPs) are currently the most effective in vivo delivery systems for silencing target genes in hepatocytes employing small interfering RNA. Antigen-presenting cells (APCs) are also potential targets for LNP siRNA. We examined the uptake, intracellular trafficking, and gene silencing potency in primary bone marrow macrophages (bmMΦ) and dendritic cells of siRNA formulated in LNPs containing four different ionizable cationic lipids namely DLinDAP, DLinDMA, DLinK-DMA, and DLinKC2-DMA. LNPs containing DLinKC2-DMA were the most potent formulations as determined by their ability to inhibit the production of GAPDH target protein. Also, LNPs containing DLinKC2-DMA were the most potent intracellular delivery agents as indicated by confocal studies of endosomal versus cytoplamic siRNA location using fluorescently labeled siRNA. DLinK-DMA and DLinKC2-DMA formulations exhibited improved gene silencing potencies relative to DLinDMA but were less toxic. In vivo results showed that LNP siRNA systems containing DLinKC2-DMA are effective agents for silencing GAPDH in APCs in the spleen and peritoneal cavity following systemic administration. Gene silencing in APCs was RNAi mediated and the use of larger LNPs resulted in substantially reduced hepatocyte silencing, while similar efficacy was maintained in APCs. These results are discussed with regard to the potential of LNP siRNA formulations to treat immunologically mediated diseases.