E10i-494 is a branched ionizable lipid designed to enhance the delivery of mRNA and CRISPR-Cas9 ribonucleoprotein (RNP) complexes. It belongs to the Branched Endosomal Disruptor (BEND) lipid family, which features terminal branching to improve endosomal escape and cellular uptake.E10i-494 demonstrated exceptional performance in T cell engineering, achieving >80% transfection efficiency in primary human T cells. This is significantly higher than the ~70% efficiency achieved by the linear lipid C14-494.The isopropyl branch enhances the lipid's ability to penetrate and disrupt endosomal membranes, leading to improved release of mRNA and RNPs into the cytoplasm.Despite its high efficiency, E10i-494 exhibits low cytotoxicity, making it suitable for therapeutic applications.E10i-494 is particularly effective for delivering mRNA to T cells, making it a promising tool for CAR-T cell therapy and other immunotherapies.Its ability to deliver CRISPR-Cas9 RNPs efficiently also makes it suitable for in vivo gene editing applications.

IAJD-34 is a one-component ionizable amphiphilic Janus dendrimer specifically engineered for targeted mRNA delivery to the lung parenchyma, as described by Meshanni et al. in Nature Communications article "Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers" . This synthetic nanoparticle self-assembles with mRNA through simple mixing in acetate buffer, forming stable dendrimersomes approximately 93-97 nm in size with high encapsulation efficiency (>95%) and a positive zeta potential (~48 mV). Its defining feature, highlighted in the study, is exceptional lung tropism after intravenous injection, enabling significantly higher luciferase expression in murine lungs compared to other organs. As demonstrated by Meshanni et al., IAJD 34 effectively delivers therapeutic mRNA (e.g., TGF-β mRNA) to the lower lung, inducing transient protein production with minimal systemic toxicity at appropriate doses (e.g., 10 µg), offering a promising strategy for treating parenchymal lung diseases.

PPz-2R1 is an ionizable cationic lipid engineered for mRNA delivery via lipid nanoparticles (LNPs). These LNPs demonstrate remarkable lung-selective accumulation in mice, showing significantly higher uptake compared to heart, liver, spleen, and kidney tissues. When loaded with PTEN mRNA, PPz-2R1 LNPs effectively restore tumor suppressor function in PTEN-deficient lung cancer cells and inhibit tumor progression in orthotopic models, with enhanced efficacy observed in combination with PD-1 blockade therapy.

(+)CP-LC-0729 is an cationic lipid derived from CP-LC-0729 and achieves significantly higher expression and selectivity highlights the advantages of this lipid system for lung-targeted delivery.

FO35 is an artificial intelligence-guided designed ionizable lipid for RNA delivery to the muscle, lung and nose. FO-35 LNPs enable potent transfection throughout the whole ferret lung epithelium, from trachea to alveoli.

FO-32 is an artificial intelligence-guided designed ionizable lipid for RNA delivery to the muscle, lung and nose. FO-32 LNPs enable potent transfection throughout the whole ferret lung epithelium, from trachea to alveoli.

306-N16B is a lipidnanoparticle, and allows systemic codelivery of Cas9 mRNA and sgRNA. 306-N16B can transport mRNA to the pulmonaryendothelial cell. 306-N16B can be used for research of genome editing-based therapies. Based on the same lipid libraries with 306-O12B, the researchers also found that N-series ionizable lipids were able to selectively deliver mRNA to the lungs of mice. Compared with the liver-targeted O-series ionizable lipids which contained ester bond in lipid tail found in previous work, such as 306-O12B, the N-series ionizable lipids with the lipid tail containing amide bond prefer to deliver mRNA to the lung. As a N-series ionizable lipid, the chemical structure of the 306-N16B is shown in Figure 4a,b. The difference of organ targeting may be due to their adsorption of different protein coronas during blood circulation caused by their different structures mentioned earlier.It has shown that the second major protein of the protein corona adsorbed by liver-targeting 306-O12B iLNPs was apolipoprotein E (ApoE), while the three dominant proteins in the protein corona adsorbed by lung-targeting 306-N16B iLNPs were serum albumin, fibrinogen beta chain, and fibrinogen gamma chain. However, the 306-N16B iLNPs showed less organ selectivity when systematically codelivered Cas9 mRNA and sgRNA in vivo, which could simultaneously activate tdTomato expression in the liver and lung of Ai14 mice, whereas single mRNA delivery could almost exclusively deliver mRNA to the lungs. This surprising phenomenon requires further investigation. Both the change of iLNPs charge and the change of lipids functional group can influence the distribution of iLNPs in vivo due to the altering of protein corona composition. Therefore, it is possible to control the organ targeting of iLNPs by controlling the composition of the outer protein corona of iLNPs.

L649 is a next-generation, lung-targeting ionizable lipid specifically designed for systemic mRNA delivery developed by Hopewell. Belonging to the novel "N-series" lipid class, it features a unique structure with an amine-containing head group and hydrophobic tails incorporating amide bonds. This design enables L649 to form highly stable lipid nanoparticles (LNPs) that exhibit exceptional tropism for the lower respiratory tract (lungs, bronchi, trachea) following intravenous administration. It demonstrates superior efficiency in delivering therapeutic payloads (like mRNA) specifically to key lung cell types, including alveolar epithelial cells (AT1 and AT2) and bronchial cells, while minimizing off-target accumulation in organs like the liver. L649-based LNPs, particularly when formulated with helper lipids like POPE, combine high potency with significantly improved tolerability, allowing for effective dosing in vivo. This makes L649 a promising candidate for developing treatments for various lung diseases such as pulmonary fibrosis, COPD, lung cancer, and infectious diseases like COVID-19.​

IR-117-17 (A10-LIN) is an ionizable and biodegradable lipid specifically designed for nebulized mRNA delivery. When formulated into lipid nanoparticles (LNPs), IR-117-17 demonstrates remarkable efficacy, achieving a 300-fold enhancement in lung mRNA delivery compared to the best-performing LNP previously reported. Additionally, it shows a two-fold improvement over the leading PBAE-based delivery system, with up to a 45-fold increase in mRNA delivery efficiency to the large airways.

THOR 76​​ is an ionizable lipid developed for lung-targeted mRNA delivery, synthesized via a high-throughput Ugi four-component reaction (U4CR). It combines spermine (N3, amine core), oleyl aldehyde (A2), oleic acid (C2), and a morpholine-functionalized isonitrile (D3). Remarkably, its ​​crude reaction mixture​​ outperforms purified forms in efficacy, suggesting synergistic impurities or intermediates enhance function. Formulated into lipid nanoparticles (LNPs) with cholesterol, DOPE, and PEG-lipid, THOR 76 LNPs exhibit ​​exceptional lung tropism​​ with secondary spleen affinity after intravenous administration. They efficiently transfect ​​pulmonary endothelial cells​​, enabling robust gene expression (e.g., Cre recombinase) and significant CRISPR-Cas9-mediated gene editing (1.22% at 0.1 mg/kg dose) in the lungs. With a particle size <150 nm, positive zeta potential, and >90% mRNA encapsulation, THOR 76 achieves targeted delivery while minimizing off-target effects in the liver. Its design overcomes limitations of cationic helper lipids, offering a potent, tolerable platform for treating pulmonary genetic disorders and cancers.

Lipid CAD9 (3-A2-7b is a cationic degradable (CAD) lipid. 3-A2-7b formulated LNP, LNP-CAD9, can deliver FLuc mRNA to the lungs in vivo. LNP-CAD9 co-delivering Cas9 mRNA/VEGFR2 single guide RNA (sgRNA) effectively induces VEGFR2 knock out in lung endothelial cells of female mice.

A3T2C7 (CP-LC-1495) is a biodegradable ionizable lipid featuring three β-propionate linkers and an azetidine polar head, formulated in four-component LNPs. It demonstrates exceptional lung-targeted mRNA delivery with 97.1% selectivity and high protein expression (1.21×10⁸ p/s) in mice. Its slightly positive zeta potential (~3.5 mV) correlates with lung tropism, likely mediated by protein corona enrichment of vitronectin and prothrombin. The β-propionate structure enables pH-sensitive biodegradability for enhanced endosomal escape while maintaining low cytotoxicity (>90% cell viability). This lipid enables organ-specific mRNA delivery without permanently charged additives, outperforming conventional SORT strategies in selectivity and expression efficiency.

IAJD 294 is a ​​single-component ionizable amphiphilic Janus dendrimer​​ that autonomously coassembles with mRNA via simple injection into uniform monodisperse dendrimersome nanoparticles (DNPs, 85 nm diameter, PDI<0.2), eliminating complex multi-component formulations. Its optimized ​​3,5-benzoyl ester linkage​​ and symmetric hydrophobic tails enable ​​dual-organ targeting​​: ​Spleen​​: 2.97 × 10⁷ RLU (50% of total activity) ​​Lymph nodes​​: 10⁶ RLU (10× higher than IAJD 87) through ​​partial hydrophobic interdigitation​​ (stabilizing DNPs for enhanced lymphatic uptake) and ​​pKa ~6.5​​ (facilitating endosomal escape), validating constitutional isomerism for precision delivery.

Westgene lipid 8 is a cationic lipid featuring a tertiary amine core with three alkyl chains (C1-C15) and two unsaturated C18 linoleate-like tails. Its ionizable amine enables pH-dependent charge for mRNA encapsulation in LNPs. Key structural elements include branched alkyl groups (X1/X2: C4, X3: C2) and ester-linked unsaturated R1/R2 chains, enhancing membrane fusion and endosomal escape. N Used in lipid nanoparticles (LNPs) with DOPE, cholesterol, and PEG-DMG, it demonstrates low cytotoxicity, high mRNA delivery efficiency, and spleen-targeted immune activation, making it suitable for vaccine/therapeutic delivery.

E8i-200 is a novel Branched Endosomal Disruptor (BEND) ionizable lipid, designed to enhance the efficiency of lipid nanoparticles (LNPs) in drug delivery, particularly for mRNA and protein delivery. Its unique structure, featuring terminal branching, improves endosomal escape, a critical step in the delivery of therapeutic cargo into cells.E8i-200 is designed to enhance endosomal escape, a key bottleneck in mRNA and protein delivery. Its terminal branching structure provides several advantages:Improved Endosomal Membrane Penetration: The branched structure allows E8i-200 to more effectively disrupt endosomal membranes, facilitating the release of mRNA and proteins into the cytoplasm.Enhanced Gene Editing Efficiency: E8i-200 has been shown to significantly improve the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes, enabling efficient gene editing in vivo.E8i-200 significantly enhanced mRNA expression in the liver, outperforming traditional linear lipids like C12-200 in mouse models.E8i-200 effectively delivered CRISPR-Cas9 RNP complexes, achieving high editing efficiency in the liver, surpassing that of linear lipids.E8i-200 also showed high transfection efficiency and low cytotoxicity in T cells, making it a promising candidate for CAR-T cell engineering and other immunotherapies.

F11T6 is a next-generation lipid nanoparticle (LNP) optimized for ultra-efficient neuron-targeted mRNA delivery, featuring a dual-tetrahydrofuran (THF) core and four pH-responsive acetal tails. Its unique bis-THF architecture enhances lipid bilayer stability and promotes brain-specific biodistribution, achieving ​​16.4% GFP+ neurons​​ in vivo—the highest reported among CNS-targeting LNPs. Cryo-EM reveals a compact spherical structure (Ø~150 nm) with 93.2% mRNA encapsulation efficiency, while THF-acetal synergy enables rapid endosomal escape (Pearson coefficient: 0.16 vs. 0.27 for F10T5). Preclinical studies show F11T6 leverages meningeal lymphatic transport for brain accumulation, yielding ​​13.0% neuron-specific tdTomato expression​​ in Ai14 mice, surpassing F10T5 (8.93%) and SM102 (0.1%). Mechanistically, the dual-THF core strengthens interactions with lipoprotein receptors on brain endothelial cells, whereas acetal tails undergo acid-triggered hydrolysis in endosomes, releasing mRNA into the cytoplasm. Despite slightly higher liver/spleen accumulation than F10T5, toxicology assessments confirm no hepatorenal toxicity (BUN/ALT/AST within normal ranges) or histopathological changes. Co-localization analyses demonstrate superior penetration into deep brain regions like the hippocampus, critical for treating neurodegenerative disorders. With a LogD of 12.3, F11T6 balances lipid solubility and biodegradability, outperforming clinical benchmarks in both efficiency (40× SM102) and neuron specificity. This platform holds transformative potential for delivering CRISPR-Cas9, siRNA, or neurotrophic factors, particularly in diseases demanding high-dose CNS transfection with minimal off-target effects.

H9 is a new ionizable lipid driven from AI-Guided Ionizable Lipid Engineering (AGILE) platform for mRNA delivery. H9 LNPs shows superior mRNA transfection potency compared to LNPs containing (D-Lin-MC3-DMA).

LIS10W is a sugar-alcohol-derived ionizable lipid with L-sorbitol as the precursor.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

​​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.