| DC57006 |
L319
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L319 (LIPID 319) is a novel ionizable, biodegradable lipid for delivery of short interfering RNAs (siRNAs). L319-LPN displays rapid elimination with pKa of 6.38 and also shows well tolerated up to 10 mg/kg. |
| DC153158 |
ND-O1
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ND-O1 is a novel ionizable lipid designed to improve the delivery of siRNA via lipid nanoparticles (LNPs) for treating liver fibrosis. It is derived from Lipid 5 (structurally similar to SM-102, used in COVID-19 mRNA vaccines) but incorporates an ether bond within its hydrophobic tail, a first-of-its-kind modification aimed at enhancing delivery efficiency. In Vitro Efficiency: ND-O1 LNPs (LNP-O1) showed significantly higher siRNA transfection efficiency in activated fibroblasts compared to Lipid 5 LNPs (LNP-M). In Vivo Efficacy: In a CCl4-induced liver fibrosis mouse model, LNP-O1/siHSP47 (loaded with HSP47-targeting siRNA) reduced HSP47 expression by ~84%, threefold more effective than LNP-M. This led to a dramatic reduction in collagen deposition and marked improvement in liver fibrosis. Safety: The ether bond modification did not introduce additional toxicity, maintaining biocompatibility. ND-O1 represents a breakthrough in ionizable lipid design, demonstrating that strategic placement of ether bonds in hydrophobic tails can enhance LNP performance without compromising safety. Its success highlights its potential for clinical translation in RNA-based therapies for liver fibrosis and other hepatic diseases. |
| DC13058 |
E8i-200
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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. |
| DC13056 |
E4i-200
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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. |
| DC13101 |
E10i-494
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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. |
| DC67276 |
Lipid M
|
Lipid M, with a pKa of 6.75, appears to be a promising candidate for mRNA vaccine delivery due to its ability to facilitate efficient intracellular delivery and endosomal escape, which are critical for mRNA-based vaccines. The pKa value of 6.75 is particularly advantageous because it allows the lipid to remain positively charged at the slightly acidic pH of endosomes (pH ~6.0–6.5), promoting destabilization of the endosomal membrane and release of the mRNA into the cytoplasm. At physiological pH (7.4), the lipid is less charged, reducing potential toxicity and improving tolerability. |
| DC67243 |
ssPalmE
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ssPalmE is an ionizable lipid for delivering plasmid DNA into cells via forming lipid nanoparticles (LNPs). The disulfide-cleavable lipid is pH-sensitive and responsive to the intracellular environment. Delivery of pDNA encoding the solute form of VEGFR suppressed tumor growth in a mouse model with OS-RC-2 tumors (renal cell carcinoma). |
| DC67242 |
Lipid M
|
Lipid M is an ionizable lipid used to form lipid nanoparticles for delivering RNA. LNPs formulated with Lipid M delivered luciferase mRNA in mice resulting in higher protein expression compared to the benchmark lipid DLin-MC3-DMA. Lipid M LNPs delivering IgG mRNA showed prolonged expression compared to MC3 in non-human primates after intramuscular injection. LNPs formulated with Lipid M were able deliver EGFP and ciliary neurotrophic factor (CNTF) mRNA to retinal pigment epithelium (RPE) cells after intravitreal injection. Acute inflammation was not observed up to 6 hours post injection. |
| DC67241 |
4-O10b1
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4-O10b1 is an ionizable lipid used to generate lipid nanoparticles (LNPs) for delivering RNA to cells. LNPs comprised of 4-O10b1 and conjugated with the macrophage antibody F4/80 were able to delivery siRNA targeting TAK1 to RAW264.7 cells resulting in suppressed activation of NF-kB. Intranasal administration reduced lung injury in an influenza mouse model. |
| DC67219 |
Lipid 29 analogue-3
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Lipid 29 analogue-3 is an ionizable lipid designed for the delivery of RNA-based therapeutics, such as mRNA or siRNA. |
