306-N16B |CAS 2803699-70-7|DC Chemicals

Cas No.:	2803699-70-7
SMILES:	O=C(CCN(CCCN(CCCN(CCC(NCCSSCCCCCCCCCCCC)=O)CCC(NCCSSCCCCCCCCCCCC)=O)C)CCC(NCCSSCCCCCCCCCCCC)=O)NCCSSCCCCCCCCCCCC
Formula:	C₇₅H₁₅₁N₇O₄S₈
M.Wt:	1471.57
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	M. Qiu, Y. Tang, J. J. Chen, R. Muriph, Z. F. Ye, C. F. Huang, J. Evans, E. P. Henske, Q. B. Xu, Proc. Natl. Acad. Sci. U.S.A. 2022, 119, e2116271119.

Description:

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.

References:

M. Qiu, Y. Tang, J. J. Chen, R. Muriph, Z. F. Ye, C. F. Huang, J. Evans, E. P. Henske, Q. B. Xu, Proc. Natl. Acad. Sci. U.S.A. 2022, 119, e2116271119.

MSDS

Cat. No.	Product name	Field of application
DC57006	L319	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.
DC67295	Lipid MK16	MK16 is a novel blood-brain barrier (BBB)-crossing lipid nanoparticle (BLNP) platform developed for efficient mRNA delivery to the central nervous system (CNS). Designed through structure-guided optimization, MK16 lipids integrate a γ-secretase inhibitor-derived BBB-penetrating module (MK-0752) with ionizable amino lipids, enabling systemic mRNA transport into the brain.MK16 was selected from a library of 72 BBB-crossing lipids synthesized by conjugating small-molecule BBB transporters (e.g., L-DOPA, D-serine, MK-0752) with lipid tails. Structural refinements, including acetal-functionalized alkyl chains and optimized lipid-to-mRNA ratios (12.5:1 w/w), enhanced brain delivery efficiency. MK16 BLNPs exhibit a particle size of ~137 nm, 85% mRNA encapsulation, and a pKa of 6.7–6.9, facilitating endosomal escape.MK16 BLNPs cross the BBB via caveolae- and γ-secretase-mediated transcytosis, as validated by inhibitor studies. In mice, intravenous MK16 BLNPs delivered mRNA broadly to neurons (7.4% GFP+), astrocytes (9.7% GFP+), and brain endothelial cells (9.2% GFP+), outperforming FDA-approved LNPs (MC3, SM-102) by 6–8-fold in brain luminescence. Functional studies in Ai14 mice demonstrated Cre mRNA-mediated tdTomato activation across the hippocampus, thalamus, and cortex, with triple dosing doubling transfection efficiency.Cocaine Addiction: MK16-delivered ΔFosb mRNA enhanced cocaine-conditioned place preference in mice, mimicking addiction-related neural plasticity. Glioblastoma (GBM): Systemic MK16-Pten mRNA inhibited orthotopic U-118MG tumor growth, achieving 70% survival at 120 days vs. controls. Human Translation: Ex vivo human brain slices showed ΔFOSB expression in neurons (4.0%) and astrocytes (6.5%), confirming clinical potential.MK16 BLNPs exhibited minimal toxicity in multi-dose regimens, with normal blood biomarkers, cytokine levels, and histopathology. Unlike MK-0752, MK16 did NOT alter NOTCH pathway genes, mitigating off-target risks.
DC60793	LUMI-6	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
DC60789	SM-86 Analog-1	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	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)	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	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	Moderna Lipid compound 46 is an novel ionizable amine lipid used for mRNA delivery from Moderna patent WO2017049245A2
DC67216	Moderna Lipid 26（compound 26）

306-N16B (Disulpax)