| 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. |
| DC60793 |
LUMI-6
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LUMI-6, a brominated ionizable lipid developed through xAI’s LUMI-lab platform, features a unique molecular design with a bromine atom critical for enhancing mRNA delivery, outperforming its debrominated derivative, LUMI-6D. In murine models, it achieved a groundbreaking 20.3% gene editing efficiency in lung epithelial cells via inhaled delivery of CRISPR-Cas9 lipid nanoparticles (LNPs), surpassing previous records and the commonly used SM-102 LNP in pulmonary Cas9 mRNA/gRNA complex delivery. In human bronchial epithelial (HBE) cells, LUMI-6 demonstrated 1.8-fold higher mRNA transfection efficiency than LUMI-6D while maintaining comparable cytotoxicity to non-brominated lipids. Its brominated tail structure optimizes mRNA encapsulation and release, balancing high efficiency with low toxicity. Notably, LUMI-6 exhibits cellular selectivity, preferentially transfecting lung epithelial cells—such as ciliated (α-tubulin+) and club (CCSP+) cells—over endothelial cells, making it highly relevant for airway-targeted therapies like cystic fibrosis and surfactant disorders. Effective for both mRNA delivery and CRISPR-Cas9 systems, LUMI-6 represents a significant advancement in pulmonary gene therapy, addressing unmet needs in treating congenital lung diseases through epithelial cell-specific editing. As the first reported LNP to achieve over 20% editing efficiency in lung epithelium via inhalation, it underscores the power of AI-driven lipid discovery in accelerating therapeutic innovation. |
| DC67281 |
BNT-51
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| DC60789 |
SM-86 Analog-1
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SM-86 Analog-1 is a novel ionizable lipid designed to improve the delivery of RNA via lipid nanoparticles (LNPs) It is derived from SM-86,with 8 carbon within its hydrophobic tail. |
| DC60782 |
Lipid A4B4-S3
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A4B4-S3 is a novel biodegradable ionizable lipid that has been meticulously designed through modular platforms and optimized specifically for mRNA delivery. It serves as a critical component of lipid nanoparticles (LNPs) and enhances mRNA delivery efficiency by facilitating endosomal escape. The structural design of A4B4-S3 leverages the Passerini reaction, a highly efficient and modular chemical method that enables the rapid generation of diverse lipid libraries. The design focuses on optimizing the methylene units between lipid headgroups and linkages to strengthen hydrogen bonding interactions with mRNA ribophosphate complexes. This enhanced hydrogen bonding allows for more effective release of mRNA from endosomes, thereby boosting delivery efficiency. Concurrently, the structural optimization improves biodegradability, reducing potential long-term toxicity risks.
In experimental studies, A4B4-S3 has demonstrated superior gene editing efficacy in mouse liver compared to SM-102, a clinically prevalent lipid used in Moderna's COVID-19 vaccine. It also shows potential for repeat-dose protein replacement therapies, suggesting enhanced stability and safety for long-term treatment regimens. Technologically, A4B4-S3 not only provides a more efficient LNP formulation but also deepens the understanding of the relationship between structure and delivery efficiency. This offers new directions for the development of future mRNA therapeutics. In summary, A4B4-S3 represents a next-generation delivery carrier achieved through rational design and high-throughput screening strategies. Its performance enhancements and biodegradable properties position it as a promising candidate for gene therapies and vaccine applications. |
| DC153158 |
ND-O1 (SM-86 Analog-2)
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ND-O1 (SM-86 Analog-2) is a novel ionizable lipid designed to improve the delivery of siRNA via lipid nanoparticles (LNPs) for treating liver fibrosis. It is derived from SM-86 (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. |
| 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. |
| DC67217 |
Moderna Lipid 46
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Moderna Lipid compound 46 is an novel ionizable amine lipid used for mRNA delivery from Moderna patent WO2017049245A2 |
| DC67216 |
Moderna Lipid 26（compound 26）
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| DC67128 |
Lipid 29 analogue-2
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Lipid 29 analogue-2 is an ionizable lipid designed for the delivery of RNA-based therapeutics, such as mRNA or siRNA. |
