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Home > RNA Delivery > Cationic/Ionizable Lipids

Cationic/Ionizable Lipids

In the past five years, DC Chemicals has focused on research and development in the RNA delivery field, successfully developing over 500 cationic lipid structures and maintaining an inventory of over 200 cationic lipids. We collaborate with leading gene delivery companies and research institutions worldwide, and our products and services have received widespread acclaim.
DC Chemicals has accumulated substantial experience in the synthesis of lipids, particularly for highly complex lipid molecules. Our unique chemical synthesis and purification processes often circumvent patented and literature-reported routes, allowing us to design new synthetic routes that yield lipid molecules with higher purity than those reported in literature and patents. Our representative molecules, such as LP-01, SM-102, ALC-0315, and DLIN-MC3-DMA, have purities exceeding 98% as tested by CAD-HPLC, placing them among the top purity products available.We have the capability to scale production from grams to kilograms.


Cationic ionizable lipids play a major role in the LNP formulation and its ability to transfect target cells with its cargo. The ionizable lipids are used to complex negatively charged nucleic acid cargo. The mRNA-cationic lipid complex fuses with the cell membrane and is then delivered into the cytosol. To be able to play these roles efficiently, a cationic ionizable lipid must be engineered with a suitable apparent acid dissociation constant (pKa). The apparent pKa of a cationic ionizable lipid is the likely pKa at the LNP surface. Currently, the cationic ionizable lipids in FDA-approved therapeutics all have an apparent pKa between 6-7. This is crucial for the cationic ionizable lipid to maintain a neutral charge while in systemic circulation (pH above the pKa of the lipid, pH ~7.5), as well as its ability to become positively charged in the endosome (pH ~6.5) and facilitate membrane fusion and subsequent cytosolic release.
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Cat. No. Product Name Field of Application Chemical Structure
DC60934 Lipid P3B Featured
P3B is a biodegradable ionizable lipid engineered to function as a highly efficient delivery vehicle for genome-editing machinery (e.g., CRISPR-Cas9 and adenine base editors) specifically to the central nervous system (CNS). Its primary function is to encapsulate and transport large mRNA payloads across the brain-CSF interface following intrathecal administration, enabling robust and widespread gene editing in neurons and astrocytes across multiple brain regions, including the hippocampus, cortex, and thalamus. Notably, it facilitates precise single-nucleotide correction via base editing. Its targeting is intrinsically achieved by the intrathecal injection route, which localizes the nanoparticles within the cerebrospinal fluid, coupled with an optimized formulation that promotes efficient uptake and activity within CNS parenchyma while minimizing off-target exposure in peripheral organs.
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DC60880 2Ac3-C18 Featured
2Ac3-C18 is a unique ionizable lipid with a distinct degradable core structure:featuring 2 acrylate units and 3 amine groups—linked to a C18 alkyl chain. Its LNPs (formulated with DOPE/cholesterol/DMG-PEG2000) exhibit spleen-specific mRNA delivery in vivo.
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DCL0011 PA97MD101 Featured
PA97MD101 is an ester-containing ionizable lipid with a tetraethylenepentamine-derived headgroup and two branched hydrophobic ester arms. Identified through machine-learning-guided screening and independent animal validation, its LNPs produced approximately fourfold higher hepatic luciferase expression than SM-102 in mice after intravenous Fluc mRNA delivery at 0.1 mg/kg. The study also demonstrated Cre-dependent liver recombination and Cas9/sgTtr-mediated TTR suppression.
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DCL0020 Lipid-392 Featured
Lipid-392 is a hydrazide-linked ionizable lipid with three tertiary amines, three palmitoyl-containing branches and a hydroxyl-bearing C10 arm. It is the carrier lipid in an optimized, cholesterol-free simplified targeted lipid nanoparticle (stLNP) containing Lipid-392, POPE and DMG-PEG2000 at 90:8.5:1.5 mol%. In mice, this formulation produced 4.93-fold greater lung luciferase expression than DOTAP-5-LNP at 0.25 mg/kg intravenous mRNA dosing, with approximately 99% of the measured lung/liver/spleen expression signal in the lung. The study also demonstrated lung-cell Cre reporter activation, adenine base editing, siRNA-mediated gene silencing and IL-10 mRNA delivery in an acute lung injury model. These preclinical results support evaluation for pulmonary RNA delivery; activity depends on formulation, payload and experimental conditions.
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DCL0019 CQ-12 Featured
CQ-12 (CQ12) is a chloroquine-derived, autophagy-inhibitory lipidoid containing a 7-chloroquinoline headgroup and a hydroxyl-bearing C12 lipid chain. It was selected from the CQ6–CQ18 series for incorporation into autolysosomal degradation-inhibitory lipid nanoparticles (AUDI-LNPs). Replacing 30% of the SM-102 molar fraction with CQ-12 produced a five-component formulation containing 15 mol% CQ-12 and increased luciferase expression approximately 5.3-fold in HEK293T cells under the reported conditions. The study also evaluated CQ-12-substituted MC3 and ALC-0315 formulations, subcutaneous and intravenous mRNA delivery, and local intratracheal delivery. IL-10 and TGF-β mRNA formulations were investigated in mouse models of psoriasis and acute lung injury, respectively. CQ-12 supports research into autophagy-modulating LNPs and cytokine mRNA delivery.
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DCL0018 A18B8C14 Featured
A18B8C14 is an α-branched amine ionizable lipid developed using the photochemistry-based ionizable lipid library (PILL) platform. Its structure contains two secondary amines linked by a pentamethylene spacer and two ester-containing branched hydrophobic arms. A18B8C14 was identified as a lead for mRNA delivery; the publication reports higher in vivo expression with its optimized LNP formulation than with an MC3-based benchmark. The supporting information documents intravenous reporter-mRNA delivery, formulation screening, cellular uptake and endosomal colocalization, particle stability, and dose-dependent blood chemistry.
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DCL0017 DA lipid Featured
DA lipid is a dopamine-derived ionizable lipid incorporating a catechol antioxidant headgroup, one tertiary amine and two ester-linked branched hydrophobic tails. In the cited study, DA lipid and DA lipid nanoparticles scavenged reactive oxygen species more effectively than their oxidized ODA counterparts.
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DCL0016 U-510 Featured
U-510 is a three-tail Janus dendritic ionizable lipid containing an N-methyl tertiary amine, a hydroxypropyl head segment, an ester linker and three C8 ether-linked hydrophobic tails. In an intravenous luciferase-mRNA study in BALB/c mice, it showed a spleen-biased organ-expression profile within the U-509–U-512 series. The authors reported 52% spleen-targeting efficiency in the context of liver and spleen luminescence at 3 hours after 0.5 mg/kg mRNA; this is not a percentage of transfected spleen cells or injected dose. The U-510 LNP formulation had a reported size of 113 nm, PDI of 0.146, apparent LNP pKa of 6.38 and encapsulation efficiency of 87.88%. It supports preclinical evaluation of splenic mRNA expression rather than maximum whole-animal expression.
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DCL0015 U-503 Featured
U-503 is a Janus dendritic ionizable lipid with two tertiary amines, two hydroxyl groups, two ester linkers and six C10 alkyl tails connected to dendritic cores through ether bonds. It was identified alongside the C8-tail analogue U-502 as a leading intravenous mRNA-expression candidate in a 16-lipid study. In BALB/c mice given 0.5 mg/kg luciferase mRNA, U-503 produced a modestly higher 3-hour expression signal than the ALC-0315 comparator under the reported formulation conditions. Its LNP formulation had a size of 114 nm, PDI of 0.122, apparent LNP pKa of 6.31 and encapsulation efficiency of 89.36%. U-503 is a preclinical research candidate for systemic mRNA delivery and matched tail-length comparisons with U-502.
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DCL0014 U-502 Featured
U-502 is a Janus dendritic ionizable lipid with two tertiary amines, two hydroxyl groups and six C8 alkyl tails attached through ether-containing dendrons and ester linkers. In a 16-lipid study, U-502 and U-503 were the leading intravenous mRNA-expression candidates, with modestly higher luciferase signals than ALC-0315 in BALB/c mice at 0.5 mg/kg mRNA and a 3-hour readout. The U-502 formulation had a reported size of 108 nm, PDI of 0.125, apparent LNP pKa of 6.36 and mRNA encapsulation efficiency of 91.83%. U-502 also underwent cell transfection, lysosomal colocalization and representative tissue-histology studies. It supports preclinical research into liver-dominant systemic mRNA delivery and headgroup–tail structure–activity relationships.
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DCL0013 iL-19 Featured
iL-19 is an aminoethoxy-functionalized ionizable lipid with a triamine scaffold, two ester linkages and four doubly branched hydrophobic tails. It was identified as the overall lead for circular RNA delivery in a 2026 JACS study. With circRNA encoding firefly luciferase, iL-19 LNPs produced approximately 28-fold higher expression than the SM-102 benchmark in C2C12 cells and approximately 2.5-fold higher expression after intramuscular administration in BALB/c mice under the reported conditions. The reported circRNA formulation uses iL-19, DSPC, cholesterol and DMG-PEG2000 at 50:10:38.5:1.5 mol%. It supports preclinical investigation of circular RNA delivery to muscle; comprehensive safety and immunogenicity evaluation remains outstanding.
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DC52025 SM-102 Featured
SM-102 is an ionizable amino lipid that has been used in combination with other lipids in the formation of lipid nanoparticles.Administration of luciferase mRNA in SM-102-containing lipid nanoparticles induces hepatic luciferase expression in mice. Formulations containing SM-102 have been used in the development of lipid nanoparticles for delivery of mRNA-based vaccines.
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DC82301 IC-8(lipid MIC5) Featured
IC8 is an ionizable cationic lipid. It has been used in combination with other lipids for the formation of lipid nanoparticles (LNPs). Immunization with severe acute respiratory coronavirus 2 (SARS-CoV-2) spike glycoprotein mRNA in IC8- and manganese-containing LNPs induces IgG responses to SARS-CoV-2 Delta and Omicron variants in mice.1 Administration of mRNA encoding B7-H3 X CD3 bispecific T cell engaging (BiTE) antibodies in IC8-containing LNPs reduces tumor growth in MV4-11 and A375 mouse xenograft models.
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DC60478 ALC-0366 Featured
ALC 0366 is an ionizable cationic lipid (pKa = 6.25) from Biontech,which is derived from ALC-0315. ALC0366 has been used as a key component of LNP to deliver BNT142, a lipid nanoparticle (LNP)-formulated RNA (RNA-LNP) encoding a T cell-engaging bispecific antibody that monovalently binds the T cell marker CD3 and bivalently binds claudin 6 (CLDN6), an oncofetal antigen that is absent from normal adult tissue but expressed on various solid tumors.
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DC67617 iChol15-C4A2 Featured
iChol15-C4A2 is a groundbreaking ionizable cholesteryl lipid, expertly designed to overcome the primary challenge of liver-centric accumulation in mRNA therapeutics. Its innovative "two-in-one" structure seamlessly integrates cholesterol with an ionizable headgroup, enabling the formation of stable, three-component Lipid Nanoparticles (Tc-LNPs).The key advantage of Tc-LNPs formulated with iChol15-CA2 is their significantly reduced adsorption of Apolipoprotein E (ApoE).This unique property directly attenuates ApoE/LDLR-mediated uptake by liver cells, dramatically shifting biodistribution toward extrahepatic tissues. Peer-validated research demonstrates a remarkable 20-50 fold increase in the spleen-to-liver mRNA expression ratio compared to standard LNPs like ALC-0315, unlocking unparalleled potential for targeting the immune system. Beyond its superior targeting capability, iChol15-C4A2 ensures high mRNA encapsulation efficiency, excellent colloidal stability, and proven biocompatibility. It offers a powerful, off-the-shelf solution to advance next-generation mRNA applications, from innovative vaccines and cancer immunotherapies to treatments for splenic disorders. Discover how iChol15-C4A2 can transform your delivery platform.
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DCL0009 Lipid 01-1 Featured
Lipid 01-1 is an ionizable lipid investigated for lipid nanoparticle delivery of mRNA encoding a CD19/CD3 bispecific T-cell engager. In WO2024131874A1, 01-1-based LNPs supported serum antibody expression and were used in a Nalm6 leukemia model with human PBMCs. A single intravenous dose of mRNA1-LNPs reduced tumor bioluminescence relative to controls and the recombinant antibody regimen tested. Its structure combines a hydroxyl-bearing diamine headgroup, a cyclobutyl substituent and two ester-linked branched hydrophobic groups.
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DCL0008 Lipid 03-135 Featured
Lipid 03-135 is an ionizable lipid investigated for lipid nanoparticle delivery of mRNA encoding a CD19/CD3 bispecific T-cell engager developed by Abogen. In WO2024131874A1, its formulation showed the highest plotted serum antibody concentrations at 24 and 48 hours among five tested lipids after a single intravenous dose of mRNA1 in NOD/SCID mice.
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DCL0007 MP2 Featured
MP2 is a methylprednisolone-derived ionizable lipid with a steroidal headgroup and three acetal-containing C8 tails. In the cited study, MP2 was formulated with DOPE, cholesterol and DMG-PEG2k for rectal mRNA delivery to inflamed colonic tissue. The MP2 formulation produced about 15-fold higher colonic luciferase signal than the study's SM102 formulation in TNBS colitis mice.
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DCL0006 BP-200-C12 Featured
BP-200-C12 is a bisphosphonate-linked ionizable lipid selected from a 21-member library in Liu et al. for local RNA delivery at mineralized tissue interfaces.
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DCL0005 Lipid 6 Featured
Lipid 6 is the lead ionizable lipid among eight candidates screened by Gao et al. for mRNA delivery to primary human immune cells. Lipid 6 LNPs were used to generate MUC1-CAR T cells ex vivo and to assess their cytotoxicity against MUC1-positive cancer cell lines in vitro. Mouse reporter-mRNA expression was studied separately; in vivo antitumor efficacy of the CAR T cells was not established.
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DC60466 Lipid H9 Featured
H9 is a new ionizable lipid driven from AI-Guided Ionizable Lipid Engineering (AGILE) platform for mRNA delivery. H9 LNPs shows superior mRNA transfection potency compared to LNPs containing (D-Lin-MC3-DMA).
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DCL0004 LC-1 Featured
LC-1 (LC-lipid-1) is an ionizable lipid identified by screening a 384-member Ugi-reaction library with a large, 5.7-kb ABE–NanoLuc mRNA cargo. The cited study evaluated LC-1 lipid nanoparticles for delivery of Cas9 and base-editing cargos to the liver, brain and lung in mice, using different formulations and administration routes.
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DC68233 ATX-95 Featured
ATX-95 is an unsaturated ionizable lipid utilized in the formulation of lipid nanoparticles for drug delivery.
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DC67653 Imidazole cholesteryl ester (ICE) Featured
Imidazole cholesterol ester (ICE) is a sterol‑based ionizable cationic lipid invented by Translate‑Bio (WO2018/089790 A1) for mRNA‑loaded lipid‑nanoparticle (LNP) pulmonary delivery. It fuses an imidazole pH‑responsive headgroup with cholesterol via ester linkage. Typically formulated as a three‑component LNP (ICE : DOPE : DMG‑PEG2K = 60 : 35 : 5 mol ratio), ICE‑LNPs achieve high mRNA encapsulation (>80‑90 %), good nebulization stability and low toxicity. Upon cellular uptake, imidazole mediates endosomal escape; the ester bond degrades to yield cholesterol, conferring favorable biocompatibility. Animal studies demonstrate robust CFTR protein expression in bronchial and alveolar lung tissue after inhalation, making ICE promising for cystic‑fibrosis mRNA therapy.
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DCL0002 HI-62 Featured
HI-62 is a cyclic-thiourea ionizable lipid reported as a lead component of onion-like multilamellar mRNA-LNPs. In the cited preprint, its E21 formulation supported high mRNA encapsulation, sustained reporter expression, frozen-storage stability and antitumor activity in a preclinical mRNA-vaccine model.
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DCL0003 Lipid 43 Featured
Lipid 43 is an ionizable lipid disclosed as Compound 43 in WO 2024/109794. In the patent's TMF30 formulation, mRNA-LNPs showed predominantly splenic reporter expression after administration in mice. Its structure, molecular formula, molecular weight and SMILES were assigned from the compound-specific synthesis scheme and checked against the reported proton count.
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DCL0001 Antioxidant lipid AO16 Featured
AO16 is a literature-reported antioxidant ionizable lipid derived from the SM-102 scaffold.
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DC60840 Lipid F10T5 Featured
F10T5 is a furan-derived ionizable lipid developed for mRNA delivery to the central nervous system through the meningeal lymphatic pathway. Its architecture incorporates an ionizable polyamine region and four hydrophobic tails containing acid-sensitive acetal linkages. Following subcutaneous administration near the deep cervical lymph nodes, F10T5 LNPs enabled functional mRNA expression in neurons, microglia, and astrocytes while producing relatively low signals in peripheral organs. Cre mRNA delivery resulted in tdTomato expression in approximately 8.93% of neurons, 7.0% of microglia, and 9.9% of astrocytes in mice. Compared with the co-lead lipid F11T6, F10T5 showed comparable total brain luciferase expression, stronger astrocyte transfection, and lower peripheral-organ distribution. Its activity was associated primarily with improved endosomal escape rather than increased cellular uptake. F10T5 remains a preclinical research lipid, and its repeat-dose safety, pharmacokinetics, and performance in larger animals require further evaluation.
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DC49932 FTT5 Featured
FTT5 is a lipid-like compound for efficient delivery of long mRNAs in vivo.
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DC68227 Lipid E20 Featured
E20 is a charge-switching ionizable lipid developed for efficient nucleic acid delivery with reduced inflammatory toxicity. Its carboxylic acid–tertiary amine headgroup changes charge between acidic formulation conditions and physiological pH, while two hydroxylated spacers and branched 8×6 hydrophobic tails support nucleic acid encapsulation and cytosolic delivery. E20 nanoparticles generated approximately 600 mU/mL serum hEPO after intravenous mRNA administration in mice. Unlike multiple benchmark LNPs, E20 did not exacerbate cytokine production in LPS-pretreated mice or human PBMCs. E20 also enabled sustained pDNA expression without the acute lethality observed with MC3-LNPs and improved IL-22 mRNA treatment in a mouse model of acute lung injury. E20 remains a preclinical research lipid.
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