MedKoo Cat#: 555308 | Name: D-Lin-MC3-DMA
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

DLin-MC3-DMA, or D-Lin-MC3-DMA, is the most potent cationic lipid that has been synthesized for lipid nanoparticles (LNPs) to deliver the siRNA. D-Lin-MC3-DMA is useful for design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA. LNP systems containing D-Lin-MC3-DMA can be highly effective, non-toxic pDNA delivery systems for gene expression both in vitro and in vivo.

Chemical Structure

D-Lin-MC3-DMA
D-Lin-MC3-DMA
CAS#1224606-06-7

Theoretical Analysis

MedKoo Cat#: 555308

Name: D-Lin-MC3-DMA

CAS#: 1224606-06-7

Chemical Formula: C43H79NO2

Exact Mass: 641.6111

Molecular Weight: 642.11

Elemental Analysis: C, 80.43; H, 12.40; N, 2.18; O, 4.98

Price and Availability

Size Price Availability Quantity
10mg USD 135.00 Ready to ship
25mg USD 225.00 Ready to ship
50mg USD 405.00 Ready to ship
100mg USD 765.00 Ready to ship
200mg USD 1,120.00 Ready to ship
500mg USD 2,450.00 Ready to ship
1g USD 4,150.00 Ready to ship
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Related CAS #
1258299-72-7 (deleted) 1224606-06-7
Synonym
D-Lin-MC3-DMA; DLin-MC3-DMA; Dlin-mc3-dma; MC 3; MC3; MC-3; RV 28; RV-28; RV28;
IUPAC/Chemical Name
(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate
InChi Key
NRLNQCOGCKAESA-KWXKLSQISA-N
InChi Code
InChI=1S/C43H79NO2/c1-5-7-9-11-13-15-17-19-21-23-25-27-29-31-33-35-38-42(46-43(45)40-37-41-44(3)4)39-36-34-32-30-28-26-24-22-20-18-16-14-12-10-8-6-2/h13-16,19-22,42H,5-12,17-18,23-41H2,1-4H3/b15-13-,16-14-,21-19-,22-20-
SMILES Code
O=C(OC(CCCCCCCC/C=C\C/C=C\CCCCC)CCCCCCCC/C=C\C/C=C\CCCCC)CCCN(C)C
Appearance
Colorless to light yellow liquid
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO (40mg/ mL) and soluble in ethanol (15mg/mL).
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
siRNA delivery vehicle
In vitro activity:
From the data in Fig. 5 A and D, the DLin-MC3-DMA/Chol system, in the absence of RNA, clearly forms a regular inverse hexagonal H2 phase at the LNP preparation conditions, pH 3 with 25% ethanol. At this condition, DLin-MC3-DMA is expected to be fully ionized (apparent pKa 6.44) (23). The addition of RNA to the LNPs, in pH 3 and 25% ethanol, decreases the order because the second-order peaks become less pronounced. This can be understood as follows: RNA (with its counterions), located inside the aqueous cylinders, screens the charges of the DLin-MC3-DMA, thereby making cylinders more flexible, i.e., decreasing their persistence length. At neutral conditions (PBS, pH 7.4, data in Fig. 5 B and E), DLin-MC3-DMA will be less ionized, and the nonionic fraction (expected to be significant at this pH) will to some extent act as a solvent, leading to a further decrease of the order in the system. In fact, this phase, when observed by polarized microscopy, is isotropic, which is also consistent with the almost perfect spherical shape of the LNPs (Fig. 2). Reference: Proc Natl Acad Sci U S A. 2018 Apr 10; 115(15): E3351–E3360. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899464/
In vivo activity:
Healthy NSG mice were injected with a therapeutic dose of 5mg/kg LNP-CTRL siRNA (LNP: lipid nanoparticle) at regular time intervals (see Figure 5A for injection schedule). CTRL or AHA1 is a targeting functional siRNA used as control, as knockdown of AHA1 has no reported phenotype. To first evaluate the uptake efficiency, injected mice were bled at regular time intervals and analyzed for the percentage and fluorescence intensity of DiI positive cells in the PB. We found that a total dose of 10 mg/kg LNP-CTRL siRNA (2 injections) resulted in a 100% uptake in peripheral blood cells, but a total dose of 15 mg/kg (3 injections over 24 hours) resulted in higher fluorescence intensity (Figure 5B and 5C, respectively). Interestingly, LNP-siRNA uptake was very stable in vivo as almost 100% peripheral blood cells were positive until day 10 after administration of the first 3 doses (Figure 5B). Peak fluorescence intensity was maintained through day 4, while DiI fluorescence intensity decreased over time (Figure 5C). Reference: Ann Hematol. 2019 Aug 1; 98(8): 1905–1918. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116733/
Solvent mg/mL mM
Solubility
DMSO 100.0 155.74
Ethanol 50.0 77.87
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 642.11 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Yanez Arteta M, Kjellman T, Bartesaghi S, Wallin S, Wu X, Kvist AJ, Dabkowska A, Székely N, Radulescu A, Bergenholtz J, Lindfors L. Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles. Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):E3351-E3360. doi: 10.1073/pnas.1720542115. Epub 2018 Mar 27. PMID: 29588418; PMCID: PMC5899464. 2. Jyotsana N, Sharma A, Chaturvedi A, Budida R, Scherr M, Kuchenbauer F, Lindner R, Noyan F, Sühs KW, Stangel M, Grote-Koska D, Brand K, Vornlocher HP, Eder M, Thol F, Ganser A, Humphries RK, Ramsay E, Cullis P, Heuser M. Lipid nanoparticle-mediated siRNA delivery for safe targeting of human CML in vivo. Ann Hematol. 2019 Aug;98(8):1905-1918. doi: 10.1007/s00277-019-03713-y. Epub 2019 May 18. PMID: 31104089; PMCID: PMC7116733.
In vitro protocol:
1. Yanez Arteta M, Kjellman T, Bartesaghi S, Wallin S, Wu X, Kvist AJ, Dabkowska A, Székely N, Radulescu A, Bergenholtz J, Lindfors L. Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles. Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):E3351-E3360. doi: 10.1073/pnas.1720542115. Epub 2018 Mar 27. PMID: 29588418; PMCID: PMC5899464.
In vivo protocol:
1. Jyotsana N, Sharma A, Chaturvedi A, Budida R, Scherr M, Kuchenbauer F, Lindner R, Noyan F, Sühs KW, Stangel M, Grote-Koska D, Brand K, Vornlocher HP, Eder M, Thol F, Ganser A, Humphries RK, Ramsay E, Cullis P, Heuser M. Lipid nanoparticle-mediated siRNA delivery for safe targeting of human CML in vivo. Ann Hematol. 2019 Aug;98(8):1905-1918. doi: 10.1007/s00277-019-03713-y. Epub 2019 May 18. PMID: 31104089; PMCID: PMC7116733.
1: Ferraresso F, Strilchuk AW, Juang LJ, Poole LG, Luyendyk JP, Kastrup CJ. Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells. Mol Pharm. 2022 Jul 4;19(7):2175-2182. doi: 10.1021/acs.molpharmaceut.2c00033. Epub 2022 May 31. PMID: 35642083; PMCID: PMC9621687. 2: Ermilova I , Swenson J . DOPC versus DOPE as a helper lipid for gene- therapies: molecular dynamics simulations with DLin-MC3-DMA. Phys Chem Chem Phys. 2020 Dec 23;22(48):28256-28268. doi: 10.1039/d0cp05111j. PMID: 33295352. 3: Ibrahim M, Gilbert J, Heinz M, Nylander T, Schwierz N. Structural insights on ionizable Dlin-MC3-DMA lipids in DOPC layers by combining accurate atomistic force fields, molecular dynamics simulations and neutron reflectivity. Nanoscale. 2023 Jul 13;15(27):11647-11656. doi: 10.1039/d3nr00987d. PMID: 37377412. 4: Algarni A, Pilkington EH, Suys EJA, Al-Wassiti H, Pouton CW, Truong NP. In vivo delivery of plasmid DNA by lipid nanoparticles: the influence of ionizable cationic lipids on organ-selective gene expression. Biomater Sci. 2022 May 31;10(11):2940-2952. doi: 10.1039/d2bm00168c. PMID: 35475455. 5: Zimmermann CM, Baldassi D, Chan K, Adams NBP, Neumann A, Porras-Gonzalez DL, Wei X, Kneidinger N, Stoleriu MG, Burgstaller G, Witzigmann D, Luciani P, Merkel OM. Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery. J Control Release. 2022 Nov;351:137-150. doi: 10.1016/j.jconrel.2022.09.021. Epub 2022 Sep 22. PMID: 36126785; PMCID: PMC7613708. 6: Kulkarni JA, Myhre JL, Chen S, Tam YYC, Danescu A, Richman JM, Cullis PR. Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA. Nanomedicine. 2017 May;13(4):1377-1387. doi: 10.1016/j.nano.2016.12.014. Epub 2016 Dec 28. PMID: 28038954. 7: Henderson MI, Eygeris Y, Jozic A, Herrera M, Sahay G. Leveraging Biological Buffers for Efficient Messenger RNA Delivery via Lipid Nanoparticles. Mol Pharm. 2022 Nov 7;19(11):4275-4285. doi: 10.1021/acs.molpharmaceut.2c00587. Epub 2022 Sep 21. PMID: 36129254; PMCID: PMC9916253. 8: Riley RS, Kashyap MV, Billingsley MM, White B, Alameh MG, Bose SK, Zoltick PW, Li H, Zhang R, Cheng AY, Weissman D, Peranteau WH, Mitchell MJ. Ionizable lipid nanoparticles for in utero mRNA delivery. Sci Adv. 2021 Jan 13;7(3):eaba1028. doi: 10.1126/sciadv.aba1028. PMID: 33523869; PMCID: PMC7806221. 9: Miao L, Lin J, Huang Y, Li L, Delcassian D, Ge Y, Shi Y, Anderson DG. Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver. Nat Commun. 2020 May 15;11(1):2424. doi: 10.1038/s41467-020-16248-y. PMID: 32415122; PMCID: PMC7229004. 10: M Bailey-Hytholt C, Ulinski G, Dugas J, Haines M, Lazebnik M, Piepenhagen P, E Zarraga I, Bandekar A. Intracellular trafficking kinetics of nucleic acid escape from lipid nanoparticles via fluorescence imaging. Curr Pharm Biotechnol. 2023 Apr 3. doi: 10.2174/1389201024666230403094238. Epub ahead of print. PMID: 37016519. 11: Yanez Arteta M, Kjellman T, Bartesaghi S, Wallin S, Wu X, Kvist AJ, Dabkowska A, Székely N, Radulescu A, Bergenholtz J, Lindfors L. Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles. Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):E3351-E3360. doi: 10.1073/pnas.1720542115. Epub 2018 Mar 27. PMID: 29588418; PMCID: PMC5899464. 12: Zhang X, Goel V, Attarwala H, Sweetser MT, Clausen VA, Robbie GJ. Patisiran Pharmacokinetics, Pharmacodynamics, and Exposure-Response Analyses in the Phase 3 APOLLO Trial in Patients With Hereditary Transthyretin-Mediated (hATTR) Amyloidosis. J Clin Pharmacol. 2020 Jan;60(1):37-49. doi: 10.1002/jcph.1480. Epub 2019 Jul 19. PMID: 31322739; PMCID: PMC6972979. 13: Biscans A, Ly S, McHugh N, Cooper DA, Khvorova A. Engineered ionizable lipid siRNA conjugates enhance endosomal escape but induce toxicity in vivo. J Control Release. 2022 Sep;349:831-843. doi: 10.1016/j.jconrel.2022.07.041. Epub 2022 Aug 3. PMID: 35917865; PMCID: PMC10281028. 14: Ermilova I, Swenson J. Ionizable lipids penetrate phospholipid bilayers with high phase transition temperatures: perspectives from free energy calculations. Chem Phys Lipids. 2023 Jul;253:105294. doi: 10.1016/j.chemphyslip.2023.105294. Epub 2023 Mar 31. PMID: 37003484. 15: Philipp J, Dabkowska A, Reiser A, Frank K, Krzysztoń R, Brummer C, Nickel B, Blanchet CE, Sudarsan A, Ibrahim M, Johansson S, Skantze P, Skantze U, Östman S, Johansson M, Henderson N, Elvevold K, Smedsrød B, Schwierz N, Lindfors L, Rädler JO. pH-dependent structural transitions in cationic ionizable lipid mesophases are critical for lipid nanoparticle function. Proc Natl Acad Sci U S A. 2023 Dec 12;120(50):e2310491120. doi: 10.1073/pnas.2310491120. Epub 2023 Dec 6. PMID: 38055742; PMCID: PMC10723131. 16: Tesei G, Hsiao YW, Dabkowska A, Grönberg G, Yanez Arteta M, Ulkoski D, Bray DJ, Trulsson M, Ulander J, Lund M, Lindfors L. Lipid shape and packing are key for optimal design of pH-sensitive mRNA lipid nanoparticles. Proc Natl Acad Sci U S A. 2024 Jan 9;121(2):e2311700120. doi: 10.1073/pnas.2311700120. Epub 2024 Jan 4. PMID: 38175863; PMCID: PMC10786277. 17: Lam K, Leung A, Martin A, Wood M, Schreiner P, Palmer L, Daly O, Zhao W, McClintock K, Heyes J. Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid-Nanoparticle Components for Therapeutic and Vaccine Applications. Adv Mater. 2023 Apr;35(15):e2209624. doi: 10.1002/adma.202209624. Epub 2023 Mar 5. PMID: 36680477. 18: Chen Z, Tian Y, Yang J, Wu F, Liu S, Cao W, Xu W, Hu T, Siegwart DJ, Xiong H. Modular Design of Biodegradable Ionizable Lipids for Improved mRNA Delivery and Precise Cancer Metastasis Delineation In Vivo. J Am Chem Soc. 2023 Nov 8;145(44):24302-24314. doi: 10.1021/jacs.3c09143. Epub 2023 Oct 19. PMID: 37853662. 19: Badri P, Habtemariam B, Melch M, Clausen VA, Arum S, Li X, Jay PY, Vest J, Robbie GJ. Pharmacokinetics and Pharmacodynamics of Patisiran in Patients with hATTR Amyloidosis and with Polyneuropathy After Liver Transplantation. Clin Pharmacokinet. 2023 Oct;62(10):1509-1522. doi: 10.1007/s40262-023-01292-w. Epub 2023 Aug 28. PMID: 37639169. 20: Nakamura T, Nakade T, Sato Y, Harashima H. Delivering mRNA to a human NK cell line, NK-92 cells, by lipid nanoparticles. Int J Pharm. 2023 Apr 5;636:122810. doi: 10.1016/j.ijpharm.2023.122810. Epub 2023 Mar 8. PMID: 36898618.

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