E10i-494
Recommended because it shares a closely related research category or delivery context. Formulation and performance are product- and study-specific.
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Components are supplied separately; this is not a premixed LNP. RNA/cargo, buffer and formulation service are not included.
4A3-SCC-PH is a biodegradable ionizable lipid investigated for liver-directed mRNA delivery. Published mouse studies report enhanced luciferase expression and extensive Cre-mediated reporter activation in hepatocytes. The detailed evidence includes formulation composition, cellular delivery, liver expression, imaging applications and tolerability.
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The 2023 JACS study separates luciferase expression, Cre reporter activation and metastatic-lesion imaging. These are distinct endpoints; the reported 99% hepatocyte result is a Cre/tdTomato reporter readout.
DC60509 corresponds to 4A3-SCC-PH. Results from 4A3-SCC-10, 4A3-SC-PH and 4A3-SSC-PH are comparator results and are not reassigned to this product.
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| 4A3-SCC-PH | DC60509 | 1948.094 | 15 | 0.463832 |
| DOPE | DC33634 | 744.03 | 15 | 0.177150 |
| Cholesterol | DCD-041 | 386.65 | 30 | 0.184119 |
| DMG-PEG2000 | DC40169 | 2507 | 3 | 0.119381 |
Source: main text and Supporting Information, LNP formulation and pKa sections. The reported 15:15:30:3 values are relative molar parts (sum 63), not mol%. Mass conversion normalizes this sum. The SI describes 40:1 using the ambiguous phrase “weight molar”; it is not treated here as a verified N/P or lipid:RNA mass ratio. DMG-PEG2000 uses MW 2507.
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-SCC-PH | ||||
| DOPE | ||||
| Cholesterol | ||||
| DMG-PEG2000 |
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Four-component LNP | 4A3-SCC-PH / DOPE / cholesterol / DMG-PEG2000 = 15:15:30:3 | Main text; SI formulation section, printed p.29 |
| RNA association | Gel-retardation and reducing-condition release assays are reported | SI Fig. S4; no numerical encapsulation percentage assigned |
| Particle properties | DLS size, zeta potential and PDI are presented graphically | SI Fig. S3; numerical batch specifications are not inferred from bars |
| Stored formulated LNP | Luciferase delivery remained measurable after one month at 4 or −20 °C | SI Fig. S16; a formulated-LNP experiment, not a pure-lipid shelf-life claim |
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| IGROV1 luciferase assay | 25 ng mRNA/well; 24 h; n = 4; 15.5-fold higher expression than MC3 reported | Main Fig. 3a and SI cell-assay methods |
| mCherry expression | 80 ng mRNA/well; fluorescence imaging and flow cytometry supported improved expression | Main Fig. 3b–c; do not substitute this dose for the luciferase assay |
| Uptake versus expression | Similar cellular uptake among tested LNPs, with different expression outputs | SI Fig. S6; uptake alone did not explain potency |
| Endosomal escape | HeLa colocalization experiments at 4 and 8 h supported improved escape | Main Fig. 4g; assay-specific mechanistic evidence, not a universal escape percentage |
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Luciferase expression | C57BL/6 mice; intravenous 0.1 mg/kg mRNA; 6 h; n = 3; 176-fold liver signal versus MC3 | Main Fig. 3g–h; study-specific signal ratio |
| Matched structural comparators | 65-fold versus 4A3-SC-PH and 14-fold versus 4A3-SSC-PH in the reported liver experiment | Main Fig. 3h; distinct compounds |
| Cre reporter | Intravenous 0.2 mg/kg Cre mRNA; analysis at 2 days; n = 3 | Main Fig. 5d–f; SI Fig. S18 and in vivo methods |
| Reported hepatocyte response | Approximately 99% tdTomato-positive hepatocytes | Cre-mediated stop-cassette removal; not a Cas9 indel frequency or disease correction rate |
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Experimental use | Fluc mRNA delivery was used to illuminate experimental metastatic lesions | Main Fig. 6; breast-cancer and melanoma models |
| Dose context | Reported imaging experiments used 0.1 mg/kg Fluc mRNA | Main Fig. 6 caption; check the panel-specific collection time |
| Readout | Bioluminescence and ex vivo tissue observations supported lesion delineation | An imaging endpoint, not tumor shrinkage or survival benefit |
| Interpretation | Reporter localization and expression were evaluated together with tumor/normal cell comparisons | Main Fig. 6; SI Figs. S20–S22 |
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Cell viability | No obvious loss of IGROV1 viability under the tested mRNA-LNP conditions | SI Figs. S1 and S5; no IC50 is assigned |
| Mouse observations | No distinct body-weight loss or obvious organ damage reported in the tested study | SI Fig. S17; histology and weight endpoints |
| Hemolysis context | Membrane-disruption assays differed between acidic and physiological pH | Main Fig. 4e–f and SI Fig. S13; acidic assay activity is not systemic safety |
| Evidence boundary | No primate or human efficacy, repeated-dose NOAEL, or batch-specific performance is established here | Use the reported mouse/cell endpoints within their study context |
Main Figs. 3, 5 and 6: cellular delivery, liver reporter activation and biological imaging — Original source figures.
Supporting Figs. S3–S5 and S16–S18: particle properties, viability, stability and tolerability — Original source figures.
| CAS No. | Not available |
| Chemical Name | 4A3-SCC-PH |
| Synonyms | 4A3-SCC-PH; 4A3 SCC PH; 4A3-SCC PH; 4A3 SCC-PH |
| SMILES | CN(CCCN(CCC(OCCSSCCOC(C(C)CSCC(CCC)CCCCC)=O)=O)CCC(OCCSSCCOC(C(C)CSCC(CCC)CCCCC)=O)=O)CCCN(CCC(OCCSSCCOC(C(C)CSCC(CCC)CCCCC)=O)=O)CCC(OCCSSCCOC(C(C)CSCC(CCC)CCCCC)=O)=O |
| Formula | C91H171N3O16S12 |
| M.Wt | 1948.094 |
| 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 |
The product molecular weight is prefilled when available and remains editable. Confirm solvent compatibility and solubility before preparation.
The reported molar ratio totals 63; normalized only for component mass calculation. N/P remains unreported.
Solvent volumes update from the molecular weight above.
| Mass | 1 mM | 5 mM | 10 mM |
|---|---|---|---|
| 10 mg | 5.1332 mL | 1.0266 mL | 513.32 μL |
| 25 mg | 12.8331 mL | 2.5666 mL | 1.2833 mL |
| 50 mg | 25.6661 mL | 5.1332 mL | 2.5666 mL |
| 100 mg | 51.3322 mL | 10.2664 mL | 5.1332 mL |
| 250 mg | 128.3306 mL | 25.6661 mL | 12.8331 mL |
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