E10i-494
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Ionizable lipid for LNP and nucleic-acid delivery research.
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. | Not available |
| Chemical Name | 4A3-SC8 |
| Synonyms | 4A3 SC8,4A3SC8 |
| 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 | 1,467.2 |
| Purity | ELSD-HPLC>95% |
| Storage | Pure form: −20 °C, 1 year; In solvent: −80 °C, 6 months; −20 °C, 1 month. Sealed and protected from light. |
| Shipping condition | Ships from Shanghai. Pure lipid is stable during ice-pack transport. |
| 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) |
The product molecular weight is prefilled when available and remains editable. Confirm solvent compatibility and solubility before preparation.
Solvent volumes update from the molecular weight above.
| Mass | 1 mM | 5 mM | 10 mM |
|---|---|---|---|
| 10 mg | 6.8157 mL | 1.3631 mL | 681.57 μL |
| 25 mg | 17.0393 mL | 3.4079 mL | 1.7039 mL |
| 50 mg | 34.0785 mL | 6.8157 mL | 3.4079 mL |
| 100 mg | 68.1570 mL | 13.6314 mL | 6.8157 mL |
| 250 mg | 170.3926 mL | 34.0785 mL | 17.0393 mL |
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