Alternate TextTo enhance service speed and avoid tariff delays, we've opened a US warehouse. All US orders ship directly from our US facility.
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.
You can also try the following methods, and our professionals will serve you Customized Consultation
Cat. No. Product Name Field of Application Chemical Structure
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.
More description
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.
More description
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.
More description
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.
More description
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.
More description
DC67291 Arcturus Lipid 54
Arcturus Lipid 54 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.
More description
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.
More description
DC60711 CL15F 9-5
CL15F 9-5, a piperidine-based ionizable lipid, exhibits favorable properties for mRNA delivery in lipid nanoparticles (LNPs). Its apparent pKa ranges between 6.24–7.15, ideal for mRNA encapsulation and endosomal escape. LNPs formulated with CL15F 9-5 (50:38.5:10:1.5 molar ratio of ionizable lipid:cholesterol:DSPC:DMG-PEG2k) demonstrated high mRNA encapsulation efficiency (>90%) and maintained physicochemical stability (size, PDI, zeta potential) during storage at 4°C for 5 months . In vitro, CL15F 9-5 LNPs showed superior luciferase expression in HEK-293T cells compared to CL4F-based LNPs. In vivo, liver-targeted LNPs delivered hEPO mRNA effectively, with sustained serum hEPO levels post-storage. Intravenous administration of FLuc mRNA-loaded CL15F 9-5 LNPs yielded strong hepatic bioluminescence, confirming liver tropism. As a vaccine candidate, CL15F 9-5 induced robust antigen-specific cellular immunity in mice, with a 14-fold increase in IFN-γ spots compared to SM-102. Its enhanced stability is attributed to reduced aldehyde impurities, minimizing mRNA-lipid adduct formation.
More description
DC85600 S14
DC60505 IR-19-Py(A20-0l)
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.
More description
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.
More description
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.
More description
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.
More description
DC60486 IAJD 288
IAJD 288(IAJD-288) is a pentaerythritol-based one-component ionizable amphiphilic Janus Dendrimer (IAJD), delivery systems for mRNA delivery.
More description
DC60840 Lipid F10T5 Featured
F10T5 is a tetrahedral tetrahydrofuran (THF)-derived lipid nanoparticle (LNP) engineered with four acid-labile acetal tails, designed for efficient mRNA delivery to the central nervous system. This lipid features a mono-THF core conjugated with branched hydrophobic chains that balance lipophilicity (LogD ≈11) and endosomal escape capability. Preclinical studies demonstrated F10T5 LNPs bypass the blood-brain barrier via meningeal lymphatic vessels (MLVs) after subcutaneous neck injection, showing 40-fold higher brain luciferase expression than FDA-approved SM102 LNPs. Cryo-EM revealed spherical nanoparticles (~170 nm diameter) with 91.9% mRNA encapsulation. In Neuro-2a cells, F10T5 exhibited superior cytoplasmic mRNA release through enhanced endosomal membrane disruption, evidenced by diffuse calcein fluorescence. Flow cytometry confirmed neuron-predicted delivery (8.8% GFP+ neurons vs 1.28% with SM102) in mice, with functional validation in Ai14 transgenic models where Cre mRNA-loaded F10T5 induced tdTomato expression in neurons and glial cells. Safety assessments showed normal hepatic/renal biomarkers and no histopathological abnormalities. The THF core and acetal tail design synergistically optimize lymphatic trafficking, brain penetration, and biodegradability, positioning F10T5 as a transformative platform for mRNA-based therapies targeting neurodegenerative diseases.
More description
DC60839 A2T2C9 (CP-LC-1465)
A2T2C9 (CP-LC-1465) is an imidazole-based ionizable lipid with branched hydrophobic chains and β-propionate linkers, formulated in four-component LNPs for spleen-targeted mRNA delivery. It achieves >80% spleen selectivity with protein expression exceeding 1×10⁷ p/s in mice, driven by its negative zeta potential (-9.7 to -19 mV). Structural features including imidazole polar head and branched acrylate (C9) enhance splenic tropism, potentially through distinct protein corona interactions. Demonstrated low cytotoxicity (>75% viability in splenic cells) and biodegradability via pH-sensitive linkers enable efficient mRNA delivery without permanent charged additives, outperforming conventional anionic SORT systems in selectivity and therapeutic potential.
More description
DC60494 76-O17Se
76-O17Se is a lipidoid for the efficient delivery of antiCD19 mRNA CAR to murine primary macrophages. 76-O17Se is more efficient than delivery with lipofectamine 2000 (LPF2K) or MC3
More description
DC60488 CL1H6
CL1H6 is an ionizable lipid designed for advanced nucleic acid delivery, and its lipid nanoparticle formulation, CL1H6-LNP, demonstrates exceptional efficiency in delivering both siRNA and mRNA into NK-92 cells. This innovative system enables precise and effective intracellular delivery, making it a valuable tool for enhancing therapeutic and research applications in natural killer cell biology.
More description
DC89101 C12-4 (Lipid A-4)
C12-4 (C12-494,Lipid A-4) 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
DC60482 DIM7S
DIM7S is a sugar-alcohol-derived ionizable lipid with mannitol as the precursor. DIM7S LNP is 10-fold, 30-fold, 20-fold, 4-fold and 3-fold superior in mRNA delivery than Lipo 3K, Electro, ALC-0315, MC3 and SM-102, respectively. DIM7S LNP enables effective CD40 mRNA delivery into human peripheral blood monocyte-derived DCs without obvious cytotoxicity.
More description
DC89030 SM-102 IMPURITY 1
DC67443 GalNAc Lipid 1002 Featured
GalNAc Lipid 1002 is a trivalent GalNAc-lipid conjugate designed for ASGPR-mediated hepatic delivery. It features a lysine-based scaffold covalently linked to three GalNAc moieties via a ​12-unit PEG spacer, anchored by a ​1,2-O-dioctadecyl-sn-glyceryl (DSG) lipid tail.
More description
DC67444 GalNAc Lipid 1005 Featured
GalNAc Lipid 1005 is a trivalent GalNAc-lipid conjugate designed for ASGPR-mediated hepatic delivery. It features a lysine-based scaffold covalently linked to three GalNAc moieties via a ​44-unit PEG spacer, anchored by a ​1,2-O-dioctadecyl-sn-glyceryl (DSG) lipid tail.
More description
DC67281 BNT-51 Featured
BNT-51 is an ionizable thiolipid developed by Biontech, characterized by its sulfur-containing moieties and a multiarm dendron-like architecture. Synthesized via reactions between amine-containing compounds and sulfur-based halides or sulfonates, it forms stable lipid nanoparticles (LNPs) optimized for mRNA delivery. The LNPs exhibit uniform particle size (80–100 nm, PDI <0.2), near-neutral zeta potential, and high mRNA encapsulation efficiency (>90%), while maintaining payload integrity through freeze-thaw cycles and extended storage. In vitro, BNT-51 demonstrates low cytotoxicity (>80% cell viability in C2C12, HepG2, and HEK293 cells) and superior transfection efficiency compared to conventional lipids, particularly in immune cells such as CD4+/CD8+ T cells within PBMCs. Its modular design allows integration of stealth lipids (e.g., PEG or vitamin E derivatives) to prolong circulation time and minimize immune activation, as evidenced by low hemolysis and complement activation risks. In vivo, BNT-51-based LNPs enable targeted mRNA delivery to splenic macrophages, achieving potent genome editing (e.g., Cre mRNA) and therapeutic protein expression (e.g., BACH1) in preclinical models. With its tunable structure, robust stability, and cell-specific tropism, BNT-51 holds promise for advancing mRNA therapeutics in gene editing, cancer immunotherapy, and regenerative medicine, offering a versatile platform for next-generation nanomedicine.
More description
DC67298 Lipid 5D8 Featured
Lipid 5D8 is a novel biodegradable ionizable lipid (IL) developed through a combinatorial chemistry strategy to overcome the limitations of conventional lipid nanoparticles (LNPs) in mRNA delivery. Synthesized via a one-step, solvent-free Michael addition reaction between amine and thiol monomers, 5D8 features asymmetric lipid tails and a biodegradable ester backbone, ensuring both structural versatility and reduced toxicity. In preclinical studies, 5D8-based LNPs demonstrated exceptional liver-targeting efficiency and mRNA delivery performance. A single intravenous dose (1 mg/kg) achieved 61% CRISPR-Cas9-mediated editing of the TTR gene in mice, reducing serum TTR protein by 90%, outperforming benchmark lipids like C12-200 (51% editing). Moreover, 5D8 enabled efficient delivery of base editors (ABE8.8 and CBE4max), achieving 42% PCSK9 editing (74% serum protein reduction) and correcting hereditary tyrosinemia in mice, significantly extending survival. Beyond gene editing, 5D8 LNPs effectively delivered siRNA (complete serum TTR clearance at 0.05 mg/kg) and enhanced hepatocyte targeting by enriching apolipoprotein E on particle surfaces. Crucially, 5D8 exhibited superior biocompatibility with no hepatotoxicity (normal ALT/AST levels), contrasting traditional LNPs. Its rapid biodegradability and "plug-and-play" design make 5D8 a versatile platform for mRNA therapeutics, holding broad potential for treating genetic disorders, cardiovascular diseases, and beyond. This innovation represents a critical advancement toward safer, high-efficiency clinical translation of gene-editing therapies.L
More description
DC60847 Moderna VC-LC-0743
VC-LC-0743 is an ionizable lipid engineered for lipid nanoparticle (LNP) delivery systems, featuring a pH-responsive morpholine/piperazine-derived headgroup that enables protonation in acidic endosomes to facilitate mRNA release. Its structure integrates a central thioether (-S-) linkage for enhanced stability, ester/amide bonds to promote enzymatic biodegradability, and branched C10-C22 alkyl chains (e.g., 2-hexyldecyl) to optimize membrane fusion and RNA encapsulation efficiency. Preclinical studies demonstrate robust in vivo transfection, achieving sustained protein expression (e.g., luciferase or antigens) at low RNA doses with minimal cytotoxicity. The lipid’s apparent pKa (~6.5-6.8) balances neutral charge at physiological pH for reduced immunogenicity and positive charge in endosomes for efficient cytosolic delivery. VC-LC-0743-based LNPs exhibit superior thermal stability (≥3 months at 4°C) and outperform commercial analogs (e.g., ALC-0315) in both potency and expression duration. Its design aligns with Formula (I) in the patent, emphasizing controlled degradation via ester/thioether cleavage to mitigate systemic toxicity. These attributes position VC-LC-0743 as a versatile candidate for mRNA vaccines, gene therapies, and targeted oncology applications, with scalable synthesis supporting clinical translation. Further studies focus on organ-specific tropism and long-term safety profiles.
More description
DC60846 Moderna VC-LC-0729
VC-LC-0729 is a structurally optimized ionizable lipid for LNPs, combining a dimethylaminoethyl headgroup for pH-sensitive charge modulation with a disulfide-thioether hybrid backbone to improve biodegradability. The lipid includes unsaturated C18 alkenyl chains (e.g., linoleyl) to enhance membrane fluidity and cellular uptake. In vitro studies reveal that VC-LC-0729 enables >90% mRNA encapsulation efficiency and sustains protein expression in hepatocytes and dendritic cells. In vivo evaluations in murine models show rapid antigen production post-administration, outperforming commercial lipids like ALC-0315 in both potency and duration of expression. The ester and thioether linkages facilitate enzymatic degradation, reducing systemic toxicity. VC-LC-0729-based LNPs also demonstrate excellent stability at -20°C for over 6 months, making them suitable for global distribution. These attributes position VC-LC-0729 as a promising candidate for mRNA vaccines and gene therapies requiring high transfection efficiency and low immunogenicity.
More description
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.​​ 
More description
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.​
More description

Customized Consultation X

Your information is safe with us. * Required Fields.

Your name
Company
Email
Procuct Name
Cat. No.
Remark
Verification code
Please fill out the characters in the picture
X