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
DC67465	Lipid 7-1 Featured	7-1 lipid represents a novel ionizable cationic compound designed for nucleic acid delivery applications. More description
DC71699	DOIC Featured	DOIC is a cationic lipid that can be used for RNA vaccines. More description
DC68146	DMDHP Featured	DMDHP ((±)-Dimyristoyl-2,3-dimethylhydroxypropylamine) is a cationic lipid with a polar head group containing a dihydroxy group. DMDHP exhibits superior transfection efficiency and lower toxicity at high DNA doses in mouse intrapulmonary transfection model. DMDHP is commonly used for gene delivery. More description
DC68145	APL-719 Featured	APL-719 is a cationic lipid that can be used to synthesize lipid nanoparticles for drug delivery. More description
DC60556	Lipid 29d Featured	Lipid 29d is an ionizable lipid containing a thiophene moiety (Thio-lipid) for mRNA delivery. Lipid 29d enables LNPs to transfect the lung and spleen. More description
DC60462	MIC1 Featured	MIC1 is a set of multi-charged lipids with four tertiary amino nitrogen atoms (4N4T) which could be constructed and applied to form novel lipid nanoparticles. 4N4T-LNPs based on MIC1 exhibit much higher mRNA translation efficiency than the approved SM-102-LNPs. 4N4T-LNPs are successfully applied to DS mRNA vaccine and the vaccines worked well against SARS-CoV-2 and its variants, including Delta and Omicron. More description
DC66654	Lipid N2-3L Featured	More description
DC67457	Lipid 1 HG3 Featured	Lipid 1 HG3 serves as a key component in LNPs specifically engineered for in vivo delivery of closed-end DNA (ceDNA), demonstrating efficient nucleic acid encapsulation and targeted release capabilities. More description
DC67119	VC1052 Featured	VC1052 is the component of Vaxfectin. Vaxfectin is a cationic lipid-based adjuvant that can be used for plasmid DNA- and protein-based vaccines. More description
DC36459	DMHAPC-Chol Featured	DMHAPC-Chol is a cationic cholesterol. Liposomes containing DMHAPC-chol have been used for DNA plasmid delivery in vitro and in vivo in a B16-F10 mouse xenograft model. Liposomes containing DMHAPC-chol are cytotoxic to B16-F10 cells. DMHAPC-Chol, as part of a lipoplex with DOPE, has also been used to deliver DNA into mouse lung via intratracheal injection, resulting in a heterogeneous distribution in the bronchi and bronchioles, and to deliver VEGF siRNA into A431 and MDA-MB-231 cells, which secrete VEGF. More description
DC71656	Vaxfectin Featured	Vaxfectin is a cationic lipid-based adjuvant that can be used for plasmid DNA- and protein-based vaccines. More description
DC67134	IM21.7c Featured	More description
DC67116	80-O14B Featured	More description
DC67490	G0-C14 analog Featured	G0-C14 analog is a derivative of the ionizable cationic lipid G0-C14. More description
DC60554	Lipid 20b Featured	Lipid 20b is a thiophene-based ionizable lipid synthesized via the Gewald reaction. It features dual unsaturated linoleic tails (C18:2) attached to the same side of the thiophene core and a tertiary amine headgroup. Formulated into LNPs (~100 nm, PDI ~0.2) with DSPC/cholesterol/DMG-PEG, it exhibits high mRNA encapsulation (>90%). Unlike traditional lipids, 20b lacks a pH-dependent ionization profile, likely due to electron delocalization in the thiophene ring. Intravenously, 20b LNPs transfect the liver and spleen in mice. Notably, subretinal delivery in mice and non-human primates (NHPs) achieved robust mRNA expression in photoreceptors (35% rods, 45% cones at high dose) and retinal pigment epithelium (RPE) with minimal acute toxicity. Immunosuppression enhanced rod transfection efficiency. High-dose administration in NHPs caused subretinal debris, but low doses (2.5 µg mRNA) maintained retinal health. This lipid demonstrates potential for liver and retinal gene therapy. More description
DC67133	C10-200 Featured	C10-200-based LNPs show enhanced liver tropism for mRNA delivery, outperforming branched-chain lipidoids (e.g., C12-200) in hepatic reporter gene expression. The system's therapeutic potential is confirmed through successful EPO production, with measurable increases in circulating protein levels following administration. More description
DC68144	Lipid G9-1 Featured	G9-1 is a nitric oxide (NO)-inhibitory ionizable lipid designed for anti-inflammatory mRNA delivery. Derived from the potent NO inhibitor G9, it retains the ability to suppress macrophage-driven inflammation while enabling efficient mRNA encapsulation and lung-targeted delivery. In a murine acute lung injury model, G9-1 lipid nanoparticles (LNPs) loaded with IL-10 mRNA demonstrated synergistic therapeutic effects by reducing inflammatory cell infiltration, suppressing pro-inflammatory cytokines, and improving systemic tissue injury markers. With its intrinsic immunomodulatory activity and preferential targeting of lung-resident cells, G9-1 represents a promising platform for safer and more effective mRNA therapeutics in inflammatory disorders. More description
DC67294	Lipid B1	Lipid B1 is a next-generation ionizable lipid engineered for superior mRNA delivery, featuring a patented β-isobutylglutarate branching linker that optimizes nanoparticle assembly and intracellular release. Its unique structure combines a pH-responsive tertiary amine headgroup with twin C18 alkyl tails connected via biodegradable ester bonds, enabling precise control over lipid packing and endosomal escape. Preclinical studies demonstrate that Lipid B1-based LNPs (bLNPs) achieve >75% transfection efficiency in vitro at ultra-low mRNA doses (1 μg), outperforming commercial benchmarks like SM-102. In vivo, subcutaneous administration of bLNPs delivers 10-fold higher luciferase expression than linear-chain analogs, with targeted biodistribution to lymph nodes and tumor sites. Clinically relevant data show 100% tumor prevention in prophylactic cancer vaccine models and 70% tumor regression in therapeutic settings when combined with checkpoint inhibitors. The ester-based backbone ensures rapid metabolic clearance, minimizing systemic toxicity risks (NOAEL >10 mg/kg in mice). Compatible with mRNA, siRNA, and CRISPR-Cas9 payloads, Lipid B1 is ideal for vaccines, gene therapies, and immuno-oncology. Its scalable 3-step synthesis (yield >80%) and lyophilization stability (-80°C, 12 months) make it a cost-effective solution for GMP-grade production. For advanced delivery with unmatched safety and efficacy, Lipid B1 sets a new standard in nucleic acid therapeutics. More description
DC67995	Lipid 22 Featured	Compound 22, as detailed in United States Patent US 2026/0014089 A1, is a bifunctional ionizable lipid engineered for precision drug delivery. Its structure integrates a monosaccharide targeting headgroup, designed to bind specifically to DC-SIGN receptors on dendritic cells, via a sophisticated linker connected to a biodegradable lipid anchor. This design enables it to serve as a key component of lipid nanoparticles (LNPs), forming a targeted delivery system. By leveraging the specific carbohydrate-receptor interaction, these LNPs are preferentially internalized by dendritic cells, critical for initiating adaptive immune responses. In vivo studies from the patent, such as the biodistribution data shown in Figure 5, confirm effective accumulation in lymphoid tissues like the spleen and lymph nodes. Consequently, this targeted delivery enhances the potency of encapsulated payloads (e.g., mRNA vaccines) by ensuring professional antigen presentation, eliciting a stronger and more specific immune response—evidenced by higher neutralizing antibody titers—making it a powerful tool for next-generation vaccines and therapeutics. More description
DC89031	SM-102 IMPURITY 2（SM-102 N-Oxide） Featured	SM-102 N-oxide is potential impurity in commercial preparations of SM-102. More description
DC60213	DOTMA Featured	N-[1-(2,3-Dioleyloxy)propyl]-N,N,N-trimethylammonium (DOTMA) is a cationic lipid.It has been used as a component in liposomes that can be used to encapsulate siRNA, microRNAs, and oligonucleotides and for gene transfection in vitro. More description
DC67563	S-Ac7-DOG Featured	S-Ac7-DOg is an ionizable lipid engineered for optimized mRNA delivery to the retina, featuring a sulfur-based ester bond (S-Ac) and dual oleyl glyceride chains (DOg). Its pKa (~6.74) is finely tuned to enhance endosomal escape in acidic environments, enabling efficient cytosolic mRNA release. Unlike traditional lipids (e.g., C12-200, MC3), S-Ac7-DOg incorporates biodegradable ester linkages that hydrolyze intracellularly, minimizing lipid accumulation and reducing innate immune activation. In vitro, S-Ac7-DOg LNPs achieved >80% transfection efficiency in retinal cells (ARPE-19, MIO-M1) with negligible cytokine secretion, outperforming MC3 and rivaling C12-200 while avoiding the latter’s high immunogenicity. In vivo, intravitreal delivery in mice showed robust protein expression in the optic nerve head (ONH) and Müller glia (75–100% of eyes), sustained for ≥7 days. Critically, it induced the lowest immunogenicity among tested lipids: minimal leukocyte infiltration (<1.5-fold vs. PBS), no microglial reactivity, and reduced GFAP upregulation. More description
DC68021	BIP-20 Featured	BiP-20 is a branched ionizable phospholipid identified as a lead compound for efficient hepatic mRNA delivery.BiP-20 is a novel, efficient, and safe liver-targeted LNP delivery vehicle. With an ideal pKa of 6.56, it achieves highly efficient liver targeting and endosomal escape primarily through the ApoE/LDL-R pathway. It demonstrates exceptional performance in gene editing at very low doses: for CRISPR-Cas9-mediated editing of TTR, a 10 μg dose achieved ~64% efficiency, which is 8-fold higher than the clinical benchmark lipid LP-01. In Prime Editing targeting the PCSK9 gene, its efficiency (4.30%) also significantly surpassed that of MC3, SM102, and LPO1. Furthermore, it mediates a 5.9-fold increase in hepatic protein expression compared to MC3. Safety assessments indicate it does not induce liver function abnormalities, showing strong therapeutic potential. More description
DC65851	CL15F6 Featured	CL15F6 is an ionizable cationic lipid (pKa = 6.75).1 It has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA and polymer-lipid hybrid nanoparticles for the delivery of plasmid DNA in vitro.1,2 More description
DC68139	Lipid M10 Featured	M10 is a piperazine-derived bis-tertiary amine ionizable lipid. With an optimal pKa of 6.56, it enables efficient liver-targeted CRISPR/Cas9 delivery, achieving durable PCSK9 silencing and LDL-C reduction after a single dose, alongside a favorable safety profile. More description
DC68138	Lipid M3 Featured	Lipid M3 is a novel ionizable lipid. Lipid M3's primary role is to enable the efficient co-encapsulation and delivery of CRISPR/Cas9 components—Cas9 mRNA and sgRNA targeting the VEGFA gene—into human retinal endothelial cells. M3 facilitates critical steps for successful gene editing, including stabilizing the nucleic acid cargo, promoting cellular uptake, and enabling effective endosomal escape to release the payload into the cytoplasm. This results in high gene-editing efficiency (indel frequency ~28.7%). A single intravitreal injection of the M3-F4 LNP carrying this CRISPR system demonstrated potent therapeutic effects in mouse models of diabetic retinopathy by significantly inhibiting pathological neovascularization and vascular leakage, while maintaining excellent biocompatibility. More description
DC68023	Lipid 1A7B13 Featured	1A7B13 is a top-performing "tripod-like" lung-targeting (LuT) lipid. It forms lipid nanoparticles (LNPs) that, after intravenous injection, deliver genetic medicines (like mRNA and CRISPR-Cas9) to the lungs with over 90% selectivity, particularly favoring epithelial cells. Compared to the benchmark DOTAP LNPs, 1A7B13 LNPs achieve a 25.5-fold increase in mRNA delivery and a 9.2-fold improvement in gene-editing efficiency within the lungs. Its therapeutic potential was demonstrated by successfully delivering IL-10 mRNA to treat acute lung injury in mice. More description
DC89101	C12-4 (Lipid A-4,Lipid F3,C12-494) Featured	C12-4 (Lipid A-4,Lipid F3) is a branched-chain ionizable cationic lipidoid that has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA. LNPs containing lipid A4 and encapsulating an mRNA reporter accumulate in the uterus, placenta, and ovaries, as well as to the spleen and liver, in pregnant mouse dams unlike LNPs containing the branched-chain ionizable cationic lipidoid C12-200, which primarily accumulate in the liver. Intravenous administration of LNPs containing lipid A4 and encapsulating mRNA encoding VEGF increase placental VEGFR1 levels and mean fetal blood vessel area without inducing liver damage in pregnant mouse dams. More description
DC68078	Lipid K9 Featured	K9 is a novel ionizable lipid designed by the multi-objective AI model MOLEA. Its core function is to enable tissue-selective mRNA delivery. When formulated into Lipid Nanoparticles (LNPs), K9 can preferentially deliver mRNA efficiently to articular chondrocytes while significantly reducing delivery to hepatocytes. This facilitates targeted drug delivery for conditions like osteoarthritis and lowers the risk of off-target effects in the liver. In vitro experiments confirm that K9-LNPs promote endosomal escape and efficient expression of mRNA in chondrocytes. Its targeted delivery efficiency is further enhanced by optimizing the LNP formulation (e.g., lipid composition ratios) using a Design of Experiment (DoE) approach. In vivo studies show that after intra-articular injection, K9-LNPs exhibit high biodistribution and gene expression in the knee joint, with limited distribution in major organs like the liver. Therefore, K9 represents an advanced, rationally designed LNP component for achieving joint tissue-specific therapy, providing a key tool for developing targeted mRNA therapeutics. More description
DC67601	Sanofi Lipid 15 Featured	Lipid 15 is the lead ionizable cationic lipid (ICL) for CD8-targeted mRNA-LNPs. As the core LNP component, Lipid 15 yields ~100 nm uniform particles with near-neutral surface charge at physiological pH, while becoming strongly cationic in acidic endosomes—reducing hepatic off-target uptake and enabling efficient endosomal escape to release mRNA. Versus other ICL candidates, Lipid 15 achieves far higher mRNA transfection efficiency in primary human CD8⁺ T cells, supports robust transient CAR expression, and triggers minimal cytokine release in immunogenicity assays. It retains structural and functional stability after freeze storage. When formulated into anti-CD8 VHH-conjugated LNPs carrying CD22 CAR mRNA, Lipid 15 drives specific in vivo reprogramming of circulating CD8⁺ T cells into functional CAR-T cells, delivering potent tumor suppression in humanized hematological malignancy models without overt toxicity. More description

Cationic/Ionizable Lipids

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