Ionizable lipids
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Lipid C24 is an ionizable lipid that can be formulated into lipid nanoparticles for delivery of RNA. Lipid C24 LNPs containing mRNA encoding SARS-CoV-2 Spike protein generated 10X higher binding and pseudoneutralizing antibodies than DLin-MC3-DMA LNPs and showed less injection site inflammation.Reference: US 2022/0218622 A1 "Ionizable lipids and methods of manufacture and use thereof"
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93-O17S is a lipidoid used for generating lipid nanoparticles to deliver RNA peptides and nucleotides. 93-O17S LNPs were able to deliver Cre recombinase mRNA in mice. In addition LNPs were able to deliver the Cre recombinase protein and Cas9:single-guide RNA into cells for genome editing. 93-O17S LNPs were used to deliver the STING pathway agonist 2′3′-Cyclic GMP-AMP (cGAMP) when injected into B16F10 tumors in mice which has potential as an in situ cancer vaccine.
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306Oi10 is a biodegradable branched chain lipidoid developed for RNA delivery in lipid nanoparticles (LNPs). Interestingly the unbranched analog was 10-fold less effective in delivering luciferase mRNA in mice. The increased potency is thought to be due to increased cone-shaped structure and protonation at endosomal pH resulting in enhanced endosomal escape. 306Oi10 has been used to co-deliver three mRNAs (firefly luciferase mCherry and erythropoietin). The LNPs derived from 306Oi10 were not immunogenic or toxic to the liver. Incorporation of DOTAP into 306Oi10 LNPs resulted in increased targeting of mRNA to pancreatic β cells via intraperitoneal injection in mice.
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ALC-0159 is a PEGylated lipid which has been used to form lipid nanoparticles for delivery of RNA. ALC-0159 is one of the components in the BNT162b2 vaccine against SARS-CoV-2 in addition to ALC-0315 DSPC and cholesterol. This is a reagent grade product for research use only. Additional information can be found here.References1) R. Tenchov R. Bird A. E. Curtze Q. Zhou (2021) “Lipid Nanoparticles—From Liposomes to mRNA Vaccine Delivery a Landscape of Research Diversity and Advancement†ACS Nano DOI: 10.1021/acsnano.1c04996.2) K.H. Moss P. Popova et al. (2019) “Lipid Nanoparticles for Delivery of Therapeutic RNA Oligonucleotides†Mol. Pharmaceutics 16 2265–2277 DOI: 10.1021/acs.molpharmaceut.8b01290.3) Y. Duan A. Dhar et al. (2020) “A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems†RSC Adv. 10 26777-26791.
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AA3-DLin is an ionizable lipid used in generating lipid nanoparticles (LNPs) for RNA delivery. Unlike LNPs formulated with other ionizable lipids AA3-DLin LNPs performed best with higher proportions of phospholipid and lower cholesterol (40:40:25:0.5 AA3-DLin/DOPE/cholesterol/DMG-PEG). AA3-DLin containing LNPs were able to deliver full-length SARS-COV2 spike protein mRNA to BALB/c mice and generate a strong immune response.
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Ionizable lipids in combination with other lipids make up the lipid nanoparticles which are used to deliver RNA-based therapeutics. cKK-E12 has been used to deliver siRNA in mice rats and primates (ED50 = 0.002 0.01 & 0.3 mg/kg respectively). It shows low toxicity and is selective for liver parenchymal cells over liver heart lung and kidney endothelial cells. This product is for research use only and not for human use. Additional information can be found here.ReferencesDong et al. (2014) Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates. PNAS Mar 18;111(11):3955-60
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DLin-MC3-DMA is an ionizable lipid used in combination with other lipids for encapsulation of RNA and DNA into lipid nanoparticles (LNPs). Administration of DLin-MC3-DMA based LNPs have delivered siRNA and reduced Factor VII levels in mice. Delivery of BCR-ABL siRNA reduced leukemic burden in a mouse model of chronic myeloid leukemia (CML).This product is for research use only and not for human use. Additional information can be found here.References1) Jayaraman M. Ansell S.M. Mui B.L. et al. (2012) “Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo." Angew. Chem. Int. Ed. Engl. 51(34) 8529-8533. DOI: 10.1002/anie. 201203263.2) Kulkarni JA Myhre JL Chen S et al. (2017) “Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA.†Nanomedicine. 13(4):1377-1387. DOI: 10.1016/j.nano.2016.12.014.3) Jyotsana N Sharma A Chaturvedi A et al. (2019) “Lipid nanoparticle-mediated siRNA delivery for safe targeting of
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DOTMA forms stable cationic liposomes in solution and can be used in the cell transfection of DNA RNA oligonucleotides anionic proteins and small peptides. DOTMA increased by at least 1000-fold the activity of an antisense oligonucleotide (ISIS 1570) in human umbilical vein endothelial cells.
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Ionizable lipids in combination with other lipids make up the lipid nanoparticles (LNPs) which are used to deliver RNA-based therapeutics. LNPs incorporating Lipid 5 (from Sabnis et al.) demonstrated potent delivery of mRNA in primates but also were rapidly cleared from the body resulting in low toxicity. Lipid 5 was better at I.V. delivery to the liver while the closely related SM-102 (cat# N-1102) was optimized for intramuscular administration. This is a reagent grade product for research use only.References:1) Sabnis S Kumarasinghe ES Salerno T et al. A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and Sustained Pharmacology and Safety in Non-human Primates. Mol Ther. 2018;26(6):1509-1519. doi:10.1016/j.ymthe.2018.03.010.2) Hassett KJ Benenato KE Jacquinet E Lee A Woods A Yuzhakov O Himansu S Deterling J Geilich BM Ketova T Mihai C Lynn A McFadyen I Moore MJ Senn JJ Stanton MG Almarsson Ö Ciaramella G Brito LA. Optimization of Lipid Nan
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Lipid A6 is an ionizable and biodegradable lipid. Lipid A6 has similar structure as Dlin-MC3-DMA but with ester and alkyne bonds to improve its biodegradability and cell membrane fusion ability. Lipid A6 forms lipid-like nanoparticles together with cKK-E12 synergistically to facilitate robust mRNA delivery with improved tolerability. MC3 is the key delivery nanoparticle component of the first siRNA drug Onpattro.
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SM-102 (Lipid H) is an ionizable lipid used in lipid nanoparticles (LNPs). LNP compositions have proven effective as transport vehicles into cells and/or intracellular compartments for biologically active substances such as small molecule drugs proteins and nucleic acids.This is a reagent grade product for research use only.
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Lipid OA2 is an ionizable lipid which can form single component lipid nanoparticles (LNPs) for delivery of RNA. Similar to lipid-based transfection reagents like LipofectamineTM pre-formed OA2 vesicles are incubated with RNA then the mixture is directly added cells. OA2 LNPs delivered siRNA to downregulate cytokine signaling 1 (SOCS1) in mouse bone marrow dentritic cells. These SOCS downregulated DCs were used as a vaccine which reduced tumor size in a B16-OVA mouse model.