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4A3-SC8

  Cat. No.:  DC82001   Featured
Chemical Structure
1857340-78-3
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More than 5000 active chemicals with high quality for research!
Field of application
4A3-SC8 is a novel Ionizable amino lipid for RNA delivery.The CRISPR-Cas9 gene editing system has been a hotspot in the field of gene therapy, especially the gene correction induced by homology-directed repair (HDR). However, its application has various obstacles, such as large molecular weight, poor stability, off-target risk, and the complexity of codeliver multiple genes. Farbiak et al. established a novel ionizable lipid library consisting of four distinct amine cores (3A3, 3A5, 4A1, 4A3) and nine peripheries with different alkyl chain lengths (SC5-SC14), and screened out a class of iLNPs with ability of encapsulating Cas9 mRNA, sgRNA and donor DNA simultaneously. The delivery efficiency (quantified by luciferase mRNA expression) and iLNPs toxicity were evaluated with three different cell lines (HEK293T, HeLa, and IGROV-1), indicating the formulation containing 4A3-SC8 was the best. 4A3-SC8 iLNPs successfully induced HDR in HEK293 cells by one-pot delivery of Cas9 mRNA, sgRNA, and the correct ssDNA template. Confocal microscopy imaging showed that a portion of blue fluorescence in cells was corrected to green fluorescence. Furthermore, the nucleic acid ratios of Cas9: sgRNA: donor DNA loading in iLNPs at a ratio of 2:1:3 could maximize the HDR efficiency with the editing efficiency up to 23%, which breaks through the current bottleneck of HDR efficiency of only 1–5%. This progress is undoubtedly an important advance in the gene therapy field to cure diseases caused by genetic mutations.
Cas No.: 1857340-78-3
Chemical Name: 4A3-SC8
SMILES: O=C(OCCOC(=O)C(C)CSCCCCCCCC)CCN(CCC(=O)OCCOC(=O)C(C)CSCCCCCCCC)CCCN(C)CCCN(CCC(=O)OCCOC(=O)C(C)CSCCCCCCCC)C CC(=O)OCCOC(=O)C(C)CSCCCCCCCC
Formula: C75H139N3O16S4
M.Wt: 1467.2
Purity: >95%
Sotrage: -20
Publication: 1 Theranostic dendrimer-based lipid nanoparticles containing PEGylated BODIPY dyes for tumor imaging and systemic mRNA delivery in vivo-Journal of Controlled Release by Hu Xionga, Shuai Liua, Tuo Weia, Qiang Chenga, Daniel J. Siegwarta||||| 2 Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery--Nature Protocols volume 18, pages265–291 (2023)
MSDS
COA
LOT NO. DOWNLOAD
2018-0101
Cat. No. Product name Field of application
DC53130 93-O17S 93-O17S is an imidazole-based synthetic lipidoid for in vivo mRNA delivery. Lipid nanoparticles (LNPs) with 93-O17S promotes both the cross-presentation of tumor antigens and the intracellular delivery of cGAMP (STING agonist).
DC59002 ssPalmO-Phe(SS-OP) ssPalmO-Phe(SS-OP) is a self-degradable material for the delivery of oligonucleotides. ssPalmO-Phe is a self-degradable derivative of ssPalm that is self-degraded in the intraparticle space by a specific hydrolytic reaction. ssPalmO-Phe is beneficial for overcoming the plasma/endosomal membrane, LNP-ssPalmO-Phe can be used to deliver both nucleic acids.
DC12381 DLin-KC2-DMA DLin-KC2-DMA is a highly potent ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of siRNA. It represents a significant advancement over earlier generations of lipids, such as DLin-DMA, due to its dramatically improved gene silencing efficiency.
DC57002 LIPID C24 C24 is a novel multiprotic ionizable lipid. C24 lipid nanoparticle (LNP) has a multistage protonation behavior resulting in greater endosomal protonation and greater translation compared to the standard reference MC3 LNP. C24 LNP also lower injection site inflammation and higher stability compared to MC3 LNP.
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.
DC67480 Sanofi Lipid VII Lipid VII is a novel ionizable cationic lipid developed by Sanofi.Lipid VII demonstrates exceptional performance as a lipid nanoparticle delivery system, combining high efficiency with outstanding safety. Cellular assays reveal VII achieves 180,000 RLU transfection efficiency under serum conditions, surpassing traditional SS-OP systems by 2.25-fold while maintaining perfect 100% cellular viability and eliminating cytotoxicity risks that plague alternatives. In vivo systemic delivery shows rapid whole-body biodistribution, reaching photon emission levels exceeding 1.00E+10 photons/sec within 48 hours. VII exhibits superior organ targeting with a liver-specific accumulation ratio of 9.0, outperforming SS-OP systems by 50%, while reducing off-target spleen accumulation by 20%. Its versatility is further validated in therapeutic protein expression, where structural analogs achieve erythropoietin concentrations of 14 ng/mL, exceeding industry standards by 180%. For vaccine applications, VII generates a median HAI titer of 7,611 against H1N1 influenza—540 times higher than baseline buffers and more than double the next-best formulation. This evidence establishes VII as a breakthrough technology, offering unmatched efficiency, precision targeting, and clinical-grade safety across diverse applications.
DC65412 Acuitas Lipid III-2 Acuitas Lipid III-2 is an ionizable amine lipid with two identical ester tails adjacent to C6 position relative to amine from patent:WO2017075531A1 with the similar activity as ALC-0315. The head of lipid is propanolamine which can effectively encapsulate mRNA used in gene therapies which depends on the availability of a safe and efficient delivery vehicle.
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.
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