E10i-494
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4A3-SC8 is an ionizable dendrimer lipid investigated for mRNA delivery. A systematic phospholipid study demonstrated formulation-dependent membrane fusion, intracellular delivery and liver-versus-spleen expression in mice.
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The 2022 phospholipid study holds 4A3-SC8, cholesterol and DMG-PEG2000 constant while changing the phospholipid. The DOPE formulation below is one defined study variant, not a universal recipe for every experiment involving this lipid.
4A3-SC8 is distinct from 4A3-SC7 and 4A3-SCC-10. Evidence from those other lipids is not assigned to DC82001.
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| 4A3-SC8 | DC82001 | 1467.2 | 38.5 | 0.564872 |
| Cholesterol | DCD-041 | 386.65 | 30 | 0.115995 |
| DOPE | DC33634 | 744.03 | 30 | 0.223209 |
| DMG-PEG2000 | DC40169 | 2507 | 1.5 | 0.037605 |
Study DOPE variant: 4A3-SC8/cholesterol/DOPE/DMG-PEG2000 = 38.5:30:30:1.5 mol%. The phospholipid was varied in parallel groups. Reported 4A3-SC8:mRNA mass ratio = 23:1; this is not total lipid:mRNA or N/P.
Prefilled proportions follow the source specified above. Molecular weights and ratios are editable. Results are calculated, not measured study data. No N/P or RNA dose is inferred.
| Component | MW | Molar ratio | Mass (mg) | Mass % |
|---|---|---|---|---|
| 4A3-SC8 | ||||
| Cholesterol | ||||
| DOPE | ||||
| DMG-PEG2000 |
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| 4A3-SC8 | DC82001 | 1467.2 | 38.5 | 0.564872 |
| Cholesterol | DCD-041 | 386.65 | 30 | 0.115995 |
| DSPC | DC57005 | 790.15 | 30 | 0.237045 |
| DMG-PEG2000 | DC40169 | 2507 | 1.5 | 0.037605 |
Same fixed molar proportions, with DSPC replacing DOPE. The biological findings show that this substitution changes performance; equivalent delivery is not assumed.
Prefilled proportions follow the source specified above. Molecular weights and ratios are editable. Results are calculated, not measured study data. No N/P or RNA dose is inferred.
| Component | MW | Molar ratio | Mass (mg) | Mass % |
|---|---|---|---|---|
| 4A3-SC8 | ||||
| Cholesterol | ||||
| DSPC | ||||
| DMG-PEG2000 |
| Study / condition | Result | Interpretation |
|---|---|---|
| Four-component variants | Approximately 100 nm; PDI <0.2; zeta potential about −2 to −4 mV | Screen-level characterization, not a batch release specification. |
| RNA encapsulation | >80% for most variants; cardiolipin variant approximately 50% | The cardiolipin result is not assigned to DOPE LNPs. |
| Storage observations | Physical characteristics followed over 72 h at room temperature and 4°C | This is not a long-term shelf-life validation. |
Main Results and Supplementary Figs. S1–S2 as described by the authors. Complete SI retrieval remains pending.
| Study / condition | Result | Interpretation |
|---|---|---|
| HEK293T and HeLa cell studies | PE-headgroup phospholipids supported higher reporter expression than the tested PC-containing comparators | Phospholipid chemistry was the experimental variable. |
| Uptake versus expression | Differences in uptake did not fully explain reporter expression | Internalization alone is an incomplete delivery endpoint. |
| DOPE versus DSPC imaging | Lower lysosomal colocalization for the DOPE formulation | Supports improved intracellular release in this comparison. |
Main Figs. 2–3; comparisons remain specific to the tested cells and formulations.
| Study / condition | Result | Interpretation |
|---|---|---|
| Endosomal-mimic liposomes | PE-containing formulations showed greater lipid fusion | Cell-free mechanistic assay. |
| DOPE and DSPC formulations | Fusion and intracellular localization supported the delivery ranking | Not a direct quantitative measurement of in vivo endosomal escape. |
| Generalization | Helper-lipid identity can alter productive delivery with the same ionizable lipid | No claim that every PE phospholipid is optimal for every RNA or tissue. |
Main Fig. 4 and associated discussion.
| Study / condition | Result | Interpretation |
|---|---|---|
| Female C57BL/6; 0.03 mg luciferase mRNA/kg IV; 6 h; n = 3 | DOPE-, POPE- and 4ME-containing LNPs gave liver-predominant expression | Reporter protein expression, not an RNA biodistribution measurement. |
| BMP phospholipid variant | Spleen-predominant expression | Lower total expression than leading PE formulations does not negate organ selectivity. |
| Separate five-component SORT experiment | 20% and 30% BMP produced spleen-selective delivery; 20% was the strongest tested setting | Different formulation series from the 38.5:30:30:1.5 screen. |
| SORT composition boundary | Results state a 15:15:30:3 base; Methods contains an extra ratio term | No prefilled SORT recipe is supplied until the SI table resolves the discrepancy. |
Main Figs. 5–6. The malformed Methods ratio is not silently treated as a validated formulation.
| Study / condition | Result | Interpretation |
|---|---|---|
| 2020 theranostic study | 4A3-SC8 with a PEGylated BODIPY co-component supported reporter delivery and tumor imaging | Different PEG component and formulation; no DMG-based recipe is inferred. |
| Tumor imaging versus treatment | Reporter expression and near-infrared imaging were measured | These endpoints do not demonstrate antitumor efficacy. |
| Safety scope | No comprehensive repeat-dose toxicity margin established by the 2022 phospholipid study | Do not import safety results from 4A3-SC7 or other related lipids. |
Álvarez-Benedicto et al. (2022); Xiong et al. (2020).
Cellular localization and membrane fusion — Figures 3–4 — Original source figures.
Organ expression and SORT comparison — Figures 5–6 — Original source figures.
| CAS No. | 1857340-78-3 |
| 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 | >95% by ELSD-HPLC |
| 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 |
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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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