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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
DC82115 BAMP-TK-12
BAMP-TK-12 is ROS‐degradable lipid used for gene/RNA delivery.
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DC60483 LIS10W
LIS10W is a sugar-alcohol-derived ionizable lipid with L-sorbitol as the precursor.
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DC88888 Lipidoid XMaN6
Lipidoid XMaN6 is an ionizable lipid with universality was screened out from the adamantyl-based ionizable lipid series, which could functionally deliver highly diverse types of nucleic acids.
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DC65427 BP-28079
Bis(N-2-ethoxyethyl 2-hexyldecanoate)amine is a cationic lipid-like PEG compound containing a polar alcohol head group, four hydrophobic tails bound by esters, and a tertiary amine linker. The hydrophilic PEG linker increases the water solubility of the compound in aqueous media. Reagent grade, for research purpose. Please contact us for GMP-grade inquiries.
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DC60670 CL4F11-ζ-2
CL4F11_ζ-2 is an ionizable lipid for hepatic delivery of CRISPR/Cas ribonucleoprotein (RNP). CL4F11_ζ-2 LNP shows an extremely strong inhibitory effect of serum TTR protein levels compared with all the approved ionizable lipids including DLin-MC3-DMA (MC3), SM-102, and ALC-0315.
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DC60662 Si6-C14b
Si6-C14b is a siloxane-incorporated lipid for livertargeting mRNA delivery. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy.
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DC13056 E4i-200
E4i-200 is a branched ionizable lipid designed for efficient mRNA and CRISPR-Cas9 delivery. It features a 4-carbon (C4) lipid tail with an isopropyl (i) branch at the terminal position, enhancing its ability to disrupt endosomal membranes. The lipid is built around the 200 core, a polyamine structure (N1-(2-(4-(2-aminoethyl)piperazin-1-yl)ethyl)ethane-1,2-diamine), which facilitates mRNA encapsulation and delivery. E4i-200 excels in liver-targeted delivery, significantly improving mRNA translation and gene editing efficiency in vivo. In experiments, it outperformed linear lipids, achieving 1.5-fold higher liver luminescence compared to the gold standard C12-200. Its isopropyl branch promotes deeper membrane penetration, enhancing endosomal escape and cargo release. This lipid is particularly effective for hepatic gene editing, reducing target gene expression (e.g., TTR) by up to 90% in mouse models. Its modular design and low toxicity make it a promising candidate for mRNA-based therapies and CRISPR applications in the liver.
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DC60686 313oi10
313oi10 is an ionizable lipid with amine headgroups which drives LNP immunogenicity by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation. 313oi10 prevents the often-observed loss of efcacy in the LNP-mediated delivery of siRNA and mRNA.
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DC60685 313O13
313O13 is an ionizable lipid with amine headgroups which drives LNP immunogenicity by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation. 313O13 prevents the often-observed loss of efcacy in the LNP-mediated delivery of siRNA and mRNA.
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DC67314 Lipid AA2
AA2 lipid is an innovative amino alcohol-derived ionizable lipid designed for optimized mRNA delivery. Its unique structure includes a hydroxyl-containing headgroup that enhances mRNA binding through hydrogen bonds and a branched ester tail (R2) that promotes a cone-shaped architecture, facilitating efficient endosomal escape. Formulated into lipid nanoparticles (LNPs) with a size of 108.6 ± 3.7 nm and a polydispersity index (PDI) below 0.3, AA2 achieves high mRNA encapsulation efficiency (89.0 ± 1.4%) and an ideal pKa of approximately 6.2, ensuring effective endosomal release.In vivo studies demonstrate that AA2 LNP-encapsulated spike mRNA elicits 4.7-fold higher IgG titers and robust CD8+ T-cell responses (characterized by IFN-γ+, TNF-α+, and granzyme B+ markers) compared to SM-102/ALC-0315 LNPs. Notably, AA2 exhibits minimal off-target accumulation, with low biodistribution in the liver and spleen. Its slightly positive surface charge (+3–5 mV) enhances cellular uptake, while the biodegradable ester structure ensures metabolic clearance, reducing potential toxicity.
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DC67290 ATX-231
ATX-231 which is from Arcturus RNA delivery platform, is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA.
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DC60505 IR-19-Py(A20-0l)
DC67519 Lipid SL01
SL01 is an ionizable cationic lipid compound pKa 6.31)developed by Seqirus, characterized by a biodegradable ester backbone and tertiary amine headgroup, enabling pH-dependent charge modulation. Its structure incorporates twin hydrophobic tails with unsaturated carbon chains, enhancing membrane fluidity and promoting endosomal escape. The lipid’s pKa (~6.5–7.0) optimizes nucleic acid complexation at physiological pH while minimizing cytotoxicity. SL01 demonstrates robust mRNA encapsulation efficiency (~90%) in lipid nanoparticles (LNPs) and facilitates intracellular delivery via endocytosis. Preclinical studies highlight its efficacy in inducing potent humoral and cellular immune responses, particularly in influenza mRNA vaccines. Its ester linkages ensure gradual metabolic clearance, reducing long-term toxicity. SL01-based LNPs exhibit stability in serum and compatibility with scalable manufacturing processes, making it a versatile candidate for therapeutic mRNA delivery.
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DC67518 Lipid SL02
SL02 is a next-generation ionizable lipid featuring a unique branched hydrophobic domain and a pH-sensitive dimethylaminoethyl headgroup(pKa 6.25)developed by Seqirus. Its asymmetric lipid tails, combining unsaturated and saturated chains, enhance LNP fusogenicity and endosomal membrane disruption. With a slightly lower pKa  than SL01, SL02 achieves efficient mRNA binding at acidic pH while maintaining neutral charge in circulation, reducing nonspecific interactions. In vitro, SL02-LNPs show superior transfection potency in BHK-V cells, attributed to improved cellular uptake and endosomal escape kinetics. In vivo, it elicits high neutralizing antibody titers (comparable to MF59-adjuvanted vaccines) and robust CD8+ T-cell activation. The lipid’s ester-based design ensures biodegradability, while PEGylation compatibility enhances colloidal stability. SL02’s tailored balance of hydrophobicity and ionization enables precise control over nanoparticle size (70–120 nm) and low polydispersity, positioning it as a leading candidate for saRNA-based vaccines and gene therapies.
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DC60797 A2C18_D5
A2C18_D5 is an optimized lipid nanoparticle (LNP) component engineered with structural modifications to enhance mRNA delivery efficiency and safety. Its design incorporates a hydrophobic head group (A2, featuring a pentyl chain) and an unsaturated C18 tail, which collectively lower its pKa to the ideal range of 6–7, enabling stable encapsulation of nucleic acids and improved endosomal escape. In vitro and in vivo studies demonstrate that A2C18_D5 achieves mRNA delivery efficiency comparable to the clinically approved LNP benchmark MC3, while exhibiting over 200-fold higher potency than its precursor lipid (A1C11). The lipid’s reduced protonation capacity minimizes cytotoxicity and hemolytic risk, aligning with safety profiles of established LNPs. Upon intravenous administration, A2C18_D5 predominantly targets the liver and spleen, with a biodistribution profile favoring hepatic delivery. Its balanced combination of high transfection efficiency, low toxicity, and favorable pharmacokinetics positions A2C18_D5 as a promising candidate for next-generation mRNA therapeutics, including vaccines and treatments for liver-specific diseases. Further optimization of its head-tail structure highlights its versatility for tailored delivery applications.
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DC67520 nor-MC3
​​nor-MC3​​ is a novel ionizable lipid develoed by Nanovation, derived from the MC3 structural framework, characterized by two ​​C17 alkyl chains​​ (each containing two Z-geometry double bonds) conjugated to a ​​4-(dimethylamino)butanoate​​ headgroup. Synthesized via a streamlined route involving Claisen condensation of methyl linoleate, hydrolysis/decarboxylation to generate a C17 ketone, reduction to the corresponding alcohol, and final esterification with 4-(dimethylamino)butanoic acid, nor-MC3 retains the ionizable amine functionality critical for pH-dependent nucleic acid binding and endosomal escape. Compared to the benchmark lipid MC3 (C18 chains), nor-MC3 demonstrates ​​superior mRNA delivery efficiency​​ in vitro (2-fold higher luciferase expression at 10 μg/mL mRNA) and enhanced in vivo biodistribution (higher liver and spleen targeting in mice). Notably, its shortened C17 chains challenge conventional assumptions about optimal hydrophobic chain length, offering improved synthetic scalability while maintaining or exceeding MC3's encapsulation efficiency (~95%), nanoparticle size (~80 nm), and low polydispersity (PDI ~0.08). For siRNA delivery, nor-MC3 achieves comparable EC₅₀ values (0.1644 μg/mL vs. MC3’s 0.1308 μg/mL), highlighting its versatility as a next-generation lipid nanoparticle (LNP) component for nucleic acid therapeutics.
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DC60486 IAJD 288
IAJD 288(IAJD-288) is a pentaerythritol-based one-component ionizable amphiphilic Janus Dendrimer (IAJD), delivery systems for mRNA delivery.
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DC89030 SM-102 IMPURITY 1
DC67522 AZD Lipid 17 Featured
Lipid 17 is a novel, highly potent ionizable lipid designed for mRNA delivery within lipid nanoparticles (LNPs) developed by AstraZeneca . Its structure features a secondary amine head group attached to a cyclic ether moiety (specifically, the 2-oxaspiro[3.3]heptan-6-amine head group). It possesses an asymmetric tail architecture: one tail is derived from heptadecan-9-ol (a branched C17 secondary alcohol), while the other tail is a modified nonyl chain (C9) with a key ethyl branch at the 3-position. The linker connecting the head group to the tails has a length equivalent to n=3 (three methylene units) as defined in the study. This specific combination of the secondary amine cyclic ether head group, asymmetric tails, and the ethyl branch at the 3-position of the nonyl chain proved critical for its exceptional performance. When formulated into LNPs and administered intravenously in mice, Lipid 17 demonstrated a remarkable 6-fold increase in functional protein (eGFP) expression in the liver compared to the benchmark lipid MC3, with high statistical significance (P < 0.0001). This makes Lipid 17 one of the most active lipids identified in the study and a promising candidate for liver-targeted mRNA therapeutics.​​ 
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DC67524 Nitto Lipid 19 Featured
Lipid 19 is an engineered cationic lipid designed to optimize the delivery of RNA within lipid nanoparticles (LNPs) developed by Nitto. Its unique structure—featuring a dual-hydroxyl headgroup and tailored hydrophobic chains—enables highly efficient encapsulation of these fragile genetic payloads, protecting them from degradation. The resulting LNPs exhibit exceptional stability (<100 nm size), target the liver specifically for enhanced therapeutic impact, and support applications ranging from mRNA vaccines to gene-silencing therapies. This makes lipid 19 a pivotal advancement in precision nanomedicine for liver-related disorders.​
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DC67531 ATX-129(ATX-0129,10q)
ATX-129 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.
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DC67535 ATX-106
ATX-106 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.
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DC67533 ATX-132
ATX-132 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.
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DC67532 ATX-111
ATX-111 is a novel ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of RNA developed by Arcturus.
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DC67541 Yoltech lipid 4
Yoltech lipid 4​​, a highly efficient ionizable lipid disclosed in patent PCT/CN2023/116607, features a central tertiary amine group flanked by hydrophobic tails—specifically, a bis(2-ethylhexyl) core and a linoleyl (C18:2) chain linked via ester bonds. This structure enables pH-responsive behavior critical for mRNA/LNP delivery: neutral in circulation (reducing toxicity) but protonated in endosomes to facilitate membrane disruption and payload release. In murine studies targeting liver PCSK9, Compound 4 achieved ​​~90% gene-editing efficiency​​. Its optimized formulation yields LNPs of ​​70–150 nm​​ with >​​90% encapsulation​​, ideal for hepatocyte-specific delivery.
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DC67539 Lipid CS22021
CS22021 is a novel, synthetically engineered ionizable sterol lipid (ISL) developed by CanSino, specifically designed for advanced mRNA delivery via lipid nanoparticles (LNPs). Its core innovation lies in its unique molecular architecture, which integrates a cholesterol moiety directly conjugated to a branched aliphatic tail (derived from ALC-0315) and a hydrophilic headgroup containing tertiary amines. This bifunctional design allows CS22021 to simultaneously fulfill the roles of both the ionizable lipid (for mRNA binding/encapsulation and endosomal escape) and the structural cholesterol component within LNPs. Consequently, CS22021 enables the formulation of highly efficient three-component LNPs (ISL-3C-LNPs), eliminating the need for free cholesterol, using only itself, the phospholipid DOPE (crucial for forming stable, uniform nanoparticles without defects), and a PEGylated lipid. When formulated into LNPs and administered intramuscularly, CS22021 demonstrates a critical property: it achieves localized mRNA expression predominantly at the injection site, significantly minimizing off-target delivery (especially to the liver/spleen) and associated systemic toxicity. Furthermore, mRNA vaccines delivered by CS22021-based LNPs elicit robust and balanced immune responses, including strong antigen-specific IgG antibodies and, notably, a significantly enhanced CD8+ T cell response compared to conventional four-component LNPs. This combination of efficient mRNA encapsulation/delivery, localized expression for improved safety, and potent induction of cellular immunity, particularly CD8+ T cells, positions CS22021 as a highly promising lipid platform, especially for next-generation mRNA vaccine applications like cancer immunotherapy.
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DC67543 ATX L2
L2 is a redox-responsive lipid engineered for ​​ultra-potent siRNA delivery​​. With shorter hexyl (C6) tails and a carbamate linker, it demonstrates the ​​fastest biodegradation​​ (liver half-life: 2.6 days) among tested lipids. L2 achieves >80% FVII gene knockdown at just 0.01 mg/kg—surpassing both L1 and MC3 in siRNA potency. Its higher apparent pKa (6.90) enhances endosomal disruption, correlating with strong in vitro hEPO expression. While slightly less effective for mRNA than L1, L2’s unmatched siRNA silencing efficiency, rapid cytosolic self-immolation, and low cytotoxicity position it as a leading candidate for RNAi therapeutics targeting hepatic diseases.
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DC67552 MeTis Lipid 5
MeTis Lipid 5 is an ​​ionizable lipid​​ featuring a ​​pyrazole-based headgroup​​ and biodegradable ​​C8-ester twin tails​​ developed by MeTis Pharmaceuticals​​ (Patent CN118290339B)​​. It demonstrated ​​breakthrough in vivo efficacy​​ (7.08E+10 photons, luciferase assay), ​​surpassing MC3 lipid by 8.8-fold​​ in systemic mRNA delivery. The molecule achieves optimal ​​safety-profile​​ (96.4% cell viability) and ​​encapsulation efficiency​​ (96.4%), forming LNPs of ​​108.9 nm (PDI 0.17)​​ at N/P 6. Its ester-enabled rapid metabolization and balanced hydrophobicity position lipid 5 as a candidate for next-gen mRNA therapeutics.
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DC67551 Lipid CDL9
CDL9​​ is an original cyclic disulfide lipid first designed, synthesized, and functionally validated in the study "In Vivo Demonstration of Enhanced mRNA Delivery by Cyclic Disulfide-Containing Lipid Nanoparticles for Facilitating Endosomal Escape" published in ​​RSC Medicinal Chemistry​​ (DOI: 10.1039/D5MD00084J).Its molecular architecture—featuring a ​​C18:2 di-unsaturated alkyl chain​​ linked to a tertiary amine headgroup modified with an α-lipoic acid-derived cyclic disulfide unit—was explicitly detailed in the paper's lipid library. Experimental data from this study demonstrated CDL9’s capacity to boost mRNA delivery efficiency by 6-fold in vitro and 5-fold in vivo when integrated into SM102-based LNPs, leveraging thiol-disulfide exchange for enhanced endosomal escape.
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DC67554 MeTis Lipid 1
MeTis Lipid 1 is an ionizable lipid featuring a pentacyclic core with geminal dimethyl groups and symmetrical C9 alkyl chains developed by Metis Pharm. According to Patent WO 2025/140421 A1, Lipid 1 demonstrated exceptional biological performance including: the highest SARS-CoV-2 neutralization titer (NT50 1:2146, 5.7-fold higher than ALC0315), potent humoral immunity with COVID-19 IgG titers reaching 1:1,000,000 post-boost and exclusive validation for VZV-gE IgG (1:1,000,000), favorable biophysical properties (124.5 nm LNP diameter, 0.2 PDI, 85% encapsulation efficiency), and excellent safety profile (hERG IC₅₀ >30 μM, Mini-Ames negative), establishing it as the lead compound in nucleic acid vaccine delivery.
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