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
DC60935	Lipid D-2 Featured	D-2 is a novel, custom-synthesized ionizable cationic lipid that serves as the core functional component of the targeted lipid nanoparticle (LNP) delivery system. Its key function is to enable the efficient in vivo delivery of therapeutic mRNAs. Under acidic conditions, it ionizes to a positive charge, allowing it to complex with and encapsulate the negatively charged mRNAs encoding the anti-FAP CAR and Lgmn protease. At physiological pH, it returns to a neutral state, which helps reduce systemic toxicity and is crucial for promoting the release of the mRNA payload inside the target macrophages within the infarcted heart. As part of the optimized LNP formulation, D-2 is fundamental for achieving high transfection efficiency, thereby enabling the in situ generation of efferocytosis-boosted CAR-Ms to treat cardiac fibrosis. More description
DC68030	C6mPhE-383 Featured	C6mPhE-383 is a top-performing ionizable lipid featuring an aromatic ring and a bioreducible disulfide bond. Formulated into lipid nanoparticles, it preferentially delivers mRNA to lymphoid tissues (lymph nodes/spleen) while minimizing off-target liver accumulation after intramuscular injection. In a SARS-CoV-2 vaccine study, it elicited strong antibody responses, promoted protective effector memory T cells, and exhibited enhanced safety by significantly reducing systemic inflammatory cytokines compared to the standard SM-102 LNP. More description
DC68022	Lipid A1F5C5 Featured	A1F5C5 is a core fluorinated ionizable lipid that forms the basis of the F5-LNP platform. Its key biological functions are multifaceted. Primarily, it enables efficient, targeted mRNA delivery in vivo. Following intravenous administration, F5-LNPs exhibit a strong tropism for the spleen and tumor sites, successfully transfecting over 70% of splenic macrophages and more than 20% of tumor-infiltrating macrophages. This allows for in situ cell engineering. Beyond delivery, A1F5C5 possesses intrinsic immunostimulatory activity. It promotes the maturation and activation of antigen-presenting cells (e.g., upregulating CD80/86 on dendritic cells) and enriches immune-related pathways like "cytokine-cytokine receptor interaction." Mechanistically, its unique 5-fluorine (F5) configuration confers superior membrane fusion capability, which is critical for efficient endosomal escape and cytosolic mRNA release. Therapeutically, when loaded with CAR mRNA, it serves as a platform for in vivo generation of CAR-macrophages (CAR-M). These CAR-M cells phagocytose tumors, reprogram the tumor microenvironment by shifting macrophages to an M1 phenotype, and activate CD8+ T cells. Notably, this approach synergizes powerfully with anti-PD-L1 therapy, achieving complete tumor regression in preclinical models. More description
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. More description
DC67657	Lipid TS41 Featured	TS41 is a trisulfide-derived ionizable lipid engineered for lipid nanoparticles (LNPs) to deliver mRNA therapeutics against multidrug-resistant bacterial pneumonia. Its optimized formulation, TS41S LNP, combines TS41 with helper lipids (e.g., DOPE, cholesterol) at a precise ratio, achieving a hydrodynamic diameter of ~105 nm, low polydispersity, and high mRNA encapsulation efficiency (~84%). This design enables efficient pulmonary delivery via intratracheal administration, with luminescence signals in lungs 4.8-fold higher than clinical benchmarks like SM-102 LNPs, ensuring targeted expression in epithelial cells, macrophages, and neutrophils. Crucially, TS41 LNPs exhibit potent anti-inflammatory properties by scavenging reactive oxygen species (ROS), reducing neutrophil infiltration and proinflammatory cytokines (e.g., IL-6, TNF-α) in infected lungs. In preclinical models, TS41S LNP encoding PB9 peptibody mRNA eradicated pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, improved survival rates to 80%, and minimized tissue damage without systemic toxicity. Its ROS-scavenging capability synergizes with antibacterial effects, offering a promising, translatable platform for combating resistant infections while controlling inflammation. Future enhancements, such as codon optimization or inhalation delivery, could further broaden its therapeutic potential. More description
DC67663	Lipid 6F Featured	6F Lipid is a Fluorinated Ionizable Lipid breakthrough in mitochondria-targeted gene delivery More description
DC67721	Macrocyclic Lipid 5 Featured	Lipid 5 is an ionizable lipid based on a macrocyclic cyclam headgroup. Its structure incorporates a benzylmethyl carbonate (BMC) linker, which contains an aromatic benzene ring, and a saturated C18 hydrophobic tail. Lipid 5 was mixed with helper lipids at a fixed molar ratio and formulated into mRNA-loaded lipid nanoparticles (LNPs) using microfluidic technology. Characterization data show that these LNPs have a hydrodynamic diameter of approximately 50-80 nanometers and a polydispersity index (PDI) below 0.2, indicating a small particle size with a uniform distribution. Their zeta potential at physiological pH is near neutral (ranging from -3 to +3 mV). The mRNA encapsulation efficiency, as determined by the Ribogreen assay, exceeds 95%. Cryo-transmission electron microscopy images reveal that the LNPs exhibit a typical spherical bilayer structure. In in vitro experiments, Lipid 5 LNPs mediated a higher level of luciferase protein expression in HEK293FT cells compared to the benchmark lipid DLin-MC3-DMA. In Balb/c mice, intravenous injection of LNPs encapsulating luciferase mRNA resulted in in vivo imaging signals predominantly concentrated in the lungs. Quantitative analysis indicated that the signal intensity in the lungs was over 100 times greater than that in the liver, with more than 95% of the total signal distributed in the lungs. In Ai9 reporter gene mice, two intravenous injections of Lipid 5 LNPs encapsulating Cre mRNA led to quantitative analysis of lung tissue sections showing that approximately 30% of lung cells were positive for tdTomato signal. More description
DC67616	GVS-18-B34	GVS-18-B34 is a highly potent, silicon ether-based ionizable lipid that enables efficient mRNA delivery via lipid nanoparticles (LNPs). Its key advantage lies in a biodegradable silyl ether linkage, which undergoes rapid, non-enzymatic hydrolysis, leading to near-complete clearance from the liver within 24 hours in both mice and non-human primates (NHPs). This degradation mechanism is species-agnostic, overcoming the variability associated with esterase-dependent lipids. In vivo, GVS-18-B34 LNPs demonstrated superior liver-specific protein expression and a high liver-to-spleen signal ratio, indicating minimal off-target accumulation and reduced immune stimulation compared to benchmarks like MC3 and SM-102. The LNPs exhibited excellent stability when stored frozen at -80°C, maintaining integrity over multiple freeze-thaw cycles. With its optimal pKa (~6.3) and efficient endosomal escape profile, GVS-18-B34 represents a promising candidate for therapeutic applications requiring frequent dosing, combining high potency with a favorable safety profile derived from its rapid clearance. More description
DC67615	STING Agonist Lipid SAL-12	SAL12 is a novel ionizable lipid derivative that integrates a non-nucleotide STING agonist (agonist 6) with an amino lipid tail through an ester bond, forming the core component of specialized lipid nanoparticles (SAL12-LNPs). These nanoparticles are designed for dual functionality: they efficiently encapsulate and deliver mRNA into dendritic cells while concurrently activating the STING pathway to stimulate innate immunity. More description
DC67618	GVS-18-B35	GVS-18-B35 is a leading silicon ether-based ionizable lipid that demonstrates exceptional performance in mRNA delivery. It features a biodegradable silyl ether linkage, which undergoes rapid, non-enzymatic hydrolysis, enabling near-complete clearance from the liver within 24 hours in both mice and non-human primates (NHPs). This degradation mechanism is independent of variable enzymatic activity, ensuring consistent pharmacokinetics across species. In vivo, GVS-18-B35 lipid nanoparticles (LNPs) achieve superior liver-specific protein expression with minimal off-target accumulation in the spleen, resulting in a high liver-to-spleen signal ratio and reduced immune stimulation. The LNPs exhibit excellent stability under frozen storage (-80°C) and maintain critical quality attributes, including particle size, polydispersity, and encapsulation efficiency, through multiple freeze-thaw cycles. With an optimal pKa (~6.3) and enhanced endosomal escape capability, GVS-18-B35 represents a robust and versatile platform for mRNA therapeutics, particularly suited for applications requiring frequent dosing due to its unique combination of high potency and rapid clearance profile. More description
DC67617	iChol15-C4A2	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. More description
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. More description
DC67633	Lipid KEL12	(4S)-KEL12 is a novel, biodegradable ionizable lipid developed for advanced mRNA vaccine delivery. It was rationally designed by incorporating both a ketal group in the linker and ester segments in the hydrophobic tails, a dual-degradable strategy aimed at enhancing its safety profile. Through iterative optimization, (4S)-KEL12 was identified as a lead candidate with an optimal pKa value of approximately 6.78, which is crucial for efficient mRNA encapsulation and endosomal release. More description
DC67632	Lipid GL5	GL5 is an ionizable guanidine-based lipid nanoparticle (G-LNP) designed for superior mRNA delivery. Its guanidinocarbonyl-pyrrole (GCP) headgroup enables pH-responsive behavior and strong mRNA binding via bidentate hydrogen bonds. The cholesterol-free GL5-3 formulation forms compact, stable nanoparticles (~90-120 nm) that exhibit excellent spleen-targeting capability after intravenous injection.GL5-LNPs efficiently deliver mRNA to antigen-presenting cells (APCs), enhancing antigen presentation and T cell activation. In cancer immunotherapy models, GL5-based mRNA vaccines provided complete tumor protection and induced durable immune memory. The platform also enables mRNA delivery to other organs like the pancreas via different administration routes, demonstrating remarkable versatility and therapeutic potential. More description
DC67651	CICL-238	Based on the data from patent US 20250127728A1, CICL-238 emerges as a highly promising ionizable lipid candidate, demonstrating notable advantages for targeted delivery applications. It achieves exceptional transfection efficiency—reaching approximately 90% of CICL-207's performance in splenic T-cells even at a reduced lipid ratio of 50% in LNP formulations. Additionally, CICL-238 exhibits minimal off-target expression in hepatocytes (<8%, comparable to CICL-207), underscoring its enhanced specificity for immune cells over liver tissues. Its optimized structure likely contributes to efficient endosomal escape and reduced Kupffer cell uptake, making it ideal for liver-related therapies (e.g., siRNA silencing for metabolic diseases) and potentially broadening applications to genetic medicine where precision and safety are paramount. Further validation in disease models could solidify its role as a versatile, low-toxicity alternative to benchmark lipids. More description
DC67654	ATX-012	ATX-012 is an ionizable cationic lipid specifically designed for mRNA delivery systems. Its unique chemical structure enables key functions in lipid nanoparticle (LNP) formulations, such as facilitating mRNA encapsulation and enhancing endosomal escape for efficient intracellular delivery. More description
DC67785	KC3-OA Featured	KC3-OA, chemically known as 3-((S)-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine, is an ionizable cationic lipid (ICL) optimized for lipid nanoparticle (LNP) formulations in nucleic acid delivery, particularly for mRNA vaccines. It features a unique structure with mono-unsaturated alkyl chains (C18:1), which enhances oxidative stability compared to polyunsaturated analogs like KC3, while maintaining efficient membrane fusion and endosomal escape capabilities. In LNP compositions, KC3-OA is typically incorporated at 46–54 mol% of total lipids, with an N/P ratio of 4–6 relative to mRNA, ensuring high encapsulation efficiency and transfection potency. Experimental data demonstrate that KC3-OA-based LNPs achieve superior mRNA expression in human dendritic cells, outperforming alternatives like KC3-PA or KC3-01 in both in vitro and in vivo models. For instance, in FIG. 2, KC3-OA LNPs showed ~2-fold higher mCherry expression at low mRNA doses (0.1 μg/mL) due to improved cellular uptake and reduced degradation. Its synergy with anionic phospholipids like DPPS (5 mol%) further enhances dendritic cell targeting via receptor-mediated internalization, leading to robust CD4+ and CD8+ T-cell responses against Mycobacterium tuberculosis antigens. This balance of stability, efficiency, and immunogenicity makes KC3-OA a leading candidate for next-generation vaccines. More description
DC67984	L31(Lipid 31) Featured	L31 is identified as a novel, proprietary ionizable cationic lipid that serves as the critical functional component within lipid nanoparticles (LNPs) engineered for CRISPR/Cas9 genome editing in head and neck squamous cell carcinoma (HNSCC). It was selected from a screened library of lipids for its superior performance. LNPs formulated with L31 exhibited excellent physicochemical properties, including a uniform size of 80-100 nm, low polydispersity, and high encapsulation efficiency (>85%) for both Cas9 mRNA and sgRNA. In vitro, L31-based LNPs demonstrated outstanding therapeutic efficacy, achieving approximately 68% gene editing of the oncogene SOX2 and an 88% reduction in cancer cell viability.For in vivo applications, L31-LNPs were further functionalized with anti-EGFR antibodies using the ASSET linker strategy to create targeted nanoparticles (tLNPs). This modification enhanced specific uptake by tumor cells. In a xenograft mouse model, intratumoral injection of these targeted L31-cLNPs co-encapsulating Cas9 mRNA and sgSOX2 led to potent tumor growth inhibition (90%) and a significant increase in survival, with tumor disappearance observed in half of the treated mice. In conclusion, L31 is a highly efficient ionizable lipid that forms the foundation of a potent targeted LNP platform for precise CRISPR-based cancer therapy against solid tumors. More description
DC67981	Diamino lipid DAL4 Featured	Diamino lipid DAL4 is diamino lipid for the preparation of lipid nanoparticles (LNPs) encapsulated with mRNAs encoding cytokines including IL-12, IL-27 and GM-CSF. Diamino lipid DAL4 delivers mRNA to tumor cells to exert anti-tumor activity. More description
DC67983	XH-07 Featured	XH-07 is an innovative ionizable cationic lipid that forms the backbone of the JCXH-211 lipid nanoparticle (LNP) delivery system. This complex is engineered to encapsulate and deliver self-replicating RNA (srRNA) encoding interleukin-12 (IL-12), a potent immunostimulatory cytokine. The LNP formulation featuring XH-07 exhibits optimal physicochemical properties, such as a mean particle size of approximately 82.12 nm with low polydispersity, and a near-neutral zeta potential around -3.181 mV, which facilitates stable circulation and efficient cellular uptake upon intravenous administration. Upon delivery, the srRNA leverages the host cell's machinery to produce sustained levels of IL-12p70, as demonstrated in B16F10 tumor-bearing mice, where a single dose led to peak cytokine production in sera and tumors. This induced IL-12 expression activates T cells and NK cells, generating a robust antitumor response. In murine models of melanoma and breast cancer, JCXH-211 monotherapy resulted in significant tumor regression and complete responses in some subjects, and it synergized with anti-PD-1 therapy to enhance efficacy. Importantly, the safety profile was acceptable, with transient liver enzyme elevations in mice that normalized quickly, and no significant adverse events in cynomolgus monkeys after repeated dosing, as evidenced by stable clinical observations and pathology tests. Thus, XH-07 is pivotal for enabling the safe and effective delivery of IL-12 encoding RNA, positioning JCXH-211 as a promising cancer immunotherapy. More description
DC67662	Lipid 48 Featured	Lipid 48 is a leading ionizable lipid designed for therapeutic nucleic acid delivery. Its key function is to form the core of lipid nanoparticles (LNPs) that efficiently encapsulate and deliver cargoes like mRNA and CRISPR guide RNAs into cells. Its optimized structure allows it to remain neutral in the bloodstream for low toxicity but become positively charged in acidic cellular compartments (endosomes), where it disrupts the membrane to release the therapeutic payload. Data from the patent demonstrates its superior profile: it achieves high gene editing efficiency (e.g., ~80% indel rates in vitro and 16.2% in vivo in mouse liver) while maintaining low cytotoxicity (cell viability >80% at effective doses), establishing it as an ideal candidate for gene therapy applications due to its exceptional balance of potency and safety. More description
DC67994	244-9-cis Featured	244-9-cis is a novel ionizable lipid disclosed in United States Patent US 2026/0014075 A1, specifically engineered for advanced lipid nanoparticle (LNP) delivery systems. Its distinctive molecular architecture features biodegradable ester bonds, which contribute to excellent physicochemical properties such as a near-neutral surface charge (approximately -3 mV) for improved biocompatibility, an optimal pKa of about 6.2 to facilitate endosomal escape, and consistently high nucleic acid encapsulation efficiency exceeding 90%. In vivo studies confirm significantly enhanced delivery to hepatocytes and markedly higher therapeutic protein expression compared to control formulations, positioning 244-9-cis as a promising candidate for next-generation genetic medicines. More description
DC60922	Lipid AP60 Featured	AP60 is a novel, biomimetic ionizable lipid, identified as the lead compound from a library of 67 aminophosphonate-derived lipids. Inspired by the structure of natural phospholipids, it forms the core component of lipid nanoparticles within the CROSS delivery platform. AP60-based LNPs demonstrate superior efficiency in delivering mRNA and circular RNA to neuronal cells and astrocytes compared to the clinically used MC3 LNP. In a mouse model of spinal cord injury, AP60 LNPs achieved significantly higher protein expression at the lesion site (13.7-fold locally, 4.6-fold intravenously) while concurrently reducing off-target accumulation in the liver by nearly 5-fold. This indicates improved targeting to the central nervous system injury site and a potentially better safety profile. Its cellular uptake is primarily mediated by clathrin-mediated endocytosis and macropinocytosis, followed by efficient endosomal escape. By encapsulating therapeutic circular RNAs encoding Sox2, Ascl1, and GDNF, AP60 LNPs enable effective in vivo reprogramming and neuroprotection, leading to significant functional recovery of bladder and locomotor functions after spinal cord injury. More description
DC68020	Lipid OC7 Featured	Lipid OC7, as described in the patent WO2022207938A1, is a novel ionizable lipid that serves as the core functional component of the saNppa-LNP delivery system. Its key innovation lies in its unique biodegradable structure featuring an internal ester bond. Under typical physiological conditions, this bond hydrolyzes, triggering a charge shift from a cationic form that complexes nucleic acids to a zwitterionic form that releases them. This property is central to its role in enabling long-acting self-amplifying RNA (saRNA) therapies. Specifically, OC7 facilitates immune stealth by mitigating early interferon responses, supports sustained and efficient intracellular replication of saRNA even at low doses, and enables therapeutic protein expression that persists for over 28 days from a single administration. This combination of efficient delivery, controlled release, and extended duration of action makes OC7-based LNPs a promising platform for long-term treatments, such as for myocardial infarction, as demonstrated in the referenced research. More description
DC66221	E12CA1A3	E12CA1A3 is an ionizable cationic lipid (pKa = 6.4) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA in vitro and in vivo.1 LNPs containing E12CA1A3 and encapsulating an mRNA reporter induce luciferase reporter expression in mouse bone marrow-derived dendritic cells (BMDCs) and mice. LNPs containing E12CA1A3 are cleared more rapidly from the liver than LNPs containing DLin-MC3-DMA (Item No. 34364) in mice. More description
DC67530	HY-501 Featured	HY-501 is a next-generation cationically ionizable lipid engineered for high-efficiency RNA delivery developed by Biontech. Formulated at 40–50 mol% in lipid nanoparticles (LNPs) alongside DSPC, cholesterol, and polysarcosine-conjugated lipid C14pSar23, HY-501 yields uniform, stable particles (80–100 nm) with >90% RNA encapsulation. It demonstrates superior in vivo performance: driving 2-fold higher protein expression than benchmark lipids (EA-405/HY-405) in muscle tissue, minimizing off-target liver accumulation, and reducing immunogenic risks (near-zero complement activation and <5% hemolysis). Preclinically, HY-501-based LNPs encoding SARS-CoV-2 spike protein elicit potent neutralizing antibodies and T-cell responses, underscoring its utility in precision vaccines. Its combination of scalable synthesis, exceptional transfection efficiency, and biosafety establishes HY-501 as a transformative vector for therapeutic RNA delivery. More description
DC82125	lipid 14 Featured	LIPID 14 is a novel ionizable lipid used for mRNA delivery.In 2021, Elia et al. used lipid 2 LNPs and lipid 14 LNPs to deliver mRNA encoding SARSCoV-2 human Fc-conjugated receptor binding domain (RBDhFc mRNA). While both lipid 274 LNP RBD-hFc mRNA and lipid 14 LNP RBD-hFc mRNA induced equal cellular and humoral responses in mice at an mRNA dose of 5 μg, only lipid 14 LNP RBD-hFc mRNA exhibited strong immunogenicity following intradermal administration. Both intradermal administration and intramuscular administration of lipid 14 LNPs could activate antigen presenting cells (APCs), thus inducing cellular responses. More description
DC67549	ORNA lipid 144（1-C）	ORNA lipid 144 is a novel ionizable lipid engineered for splenic RNA delivery developed by ORNA Therapeutics, featuring a biodegradable structure with a protonatable tertiary amine headgroup and ester-linked branched C14 alkyl chains. This design enables exceptional spleen-targeting capability, demonstrated by 3-fold higher luciferase expression in the spleen compared to benchmark lipids and near-complete B-cell depletion when delivering anti-CD19 CAR circRNA. It forms highly stable lipid nanoparticles maintaining homogeneous size (60–80 nm) and low polydispersity across diverse manufacturing conditions and buffer systems. Rapid clearance from the liver and spleen minimizes off-target accumulation, while high circRNA encapsulation efficiency (>90%) and pH-dependent endosomal escape make it ideal for immunotherapies and vaccines requiring precise splenic bioavailability and sustained efficacy. More description
DC67460	CP-LC-1422	Derived from the natural amino acid homocysteine, CP-LC-1422 is an ionizable cationic lipid that enables robust in vivo delivery of various RNA forms (mRNA, cRNA, and saRNA), driving high protein expression. When formulated into LNPs (50/38.5/10/1.5 molar ratio of ionizable lipid/cholesterol/DOPE/PEG-lipid), it achieves superior spleen-specific targeting compared to commercial options through intravenous administration, while maintaining an excellent safety profile. 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

Cationic/Ionizable Lipids

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