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DLinDMA Sale

(Synonyms: 1,2-Dilinoleyloxy-N,N-dimethyl-3-aminopropane) 目录号 : GC33476

DLinDMA 是以稳定的核酸脂质颗粒为基准的关键脂质成分。

DLinDMA Chemical Structure

Cas No.:871258-12-7

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥982.00
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50mg
¥893.00
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Sample solution is provided at 25 µL, 10mM.

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实验参考方法

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.
[2]. 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.

产品描述

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]

Chemical Properties

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
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溶解性数据

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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
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Research Update

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.