C12-200
DC58046
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Literature evidence · DC57100
Formulation & Performance
The evidence combines a patent luciferase-mRNA study with a peer-reviewed comparison of protein expression, particle properties and tolerability. Compound 9 supported liver expression, while the later comparison also identified inflammatory responses and dose-dependent tolerability limitations.
Holland et al. identify Acuitas Compound 9 in Supporting Information Figure S1 and the Compound 9 entry, with formula C57H112N2O5 and an explicit reference to US10221127B2. The illustrated connectivity matches the catalog structure. This identity does not establish that A9 is the exact lipid used in a particular clinical vaccine.
Formulation components and molecular-weight conversion
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| Acuitas A9 / Compound 9 | DC57100 | 905.51 | 50 | Not calculable from disclosed data |
| DSPC | DC57005 | 790.15 | 10 | Not calculable from disclosed data |
| Cholesterol | DCD-041 | 386.65 | 38.5 | Not calculable from disclosed data |
| PEG-DMA (ditetradecylacetamide PEG lipid) | Not uniquely mapped | Not established | 1.5 | Not calculable from disclosed data |
This table follows US10221127B2, Example 29, Table 3. Its amide-based PEG-DMA is not the PEG-DMG used in Table 2. Holland et al. later report ionizable lipid:DSPC:cholesterol:PEG lipid = 54.6:10.9:32.8:1.6 (rounded total 99.9). A specific commercial PEG identity and a single Compound 9 N/P value were not confirmed. Supporting Information Table S2 names mPEG-DMA in the GVS-18-B6 formulation, but that table is not an A9-specific post-formulation composition measurement.
Component mass calculator
Not all inputs are assigned to a single verified study formulation; unassigned fields are blank. Enter your own values to calculate a research scenario. 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 % |
|---|---|---|---|---|
| Acuitas A9 / Compound 9 | ||||
| DSPC | ||||
| Cholesterol | ||||
| PEG-DMA (ditetradecylacetamide PEG lipid) |
Patent formulation and mouse expression
| Record | Reported result | Interpretation |
|---|---|---|
| Composition | Compound 9:DSPC:cholesterol:PEG-DMA = 50:10:38.5:1.5 mol% | Example 29, Table 3; do not substitute the Table 2 PEG-DMG formulation |
| Model | Female C57BL/6 mice, 6–8 weeks; intravenous FLuc-mRNA LNP; liver readout at 4 h | Reporter-protein expression, not a clinical outcome |
| Compound 9 at 0.3 mg/kg mRNA | 2381 ± 1162 ng luciferase/g liver | Exact Table 3 row; uncertainty measure and replicate count are not defined in that table |
| Compound 9 at 1.0 mg/kg mRNA | 17157 ± 2470 ng luciferase/g liver | Same table, higher RNA dose |
| MC3 at 0.3 and 1.0 mg/kg | 603 ± 150 and 2876 ± 622 ng luciferase/g liver | Matched Table 3 comparator; Table 2 MC3 values differ |
| Apparent pKa | 6.27 | Formulated-lipid TNS assay; not an intrinsic constant of neat lipid |
US10221127B2, Examples 28–30, Table 3. The generic preparation section gives a lipid:RNA mass-ratio range, not a uniquely identified Compound 9 batch value.
Peer-reviewed formulation and particles
| Record | Reported result | Interpretation |
|---|---|---|
| Composition | Ionizable lipid:DSPC:cholesterol:PEG lipid = 54.6:10.9:32.8:1.6 | Holland et al., Methods; rounded values total 99.9 |
| Particle diameter / PDI | 90 nm / 0.06 | Table 1, complete EGFP-mRNA LNP |
| Encapsulation efficiency | 96% | Complete formulation |
| Apparent pKa | 6.20 | Different formulation/assay context from patent value 6.27 |
| Zeta potential | 2.03 mV at pH 5.5; 1.07 mV at pH 7.5 | Particle measurement |
Holland et al. ACS Nano (2024), Table 1 and LNP Production. Controlled mixing and buffer exchange are described; a unique Compound 9 N/P or mass ratio was not established from the inspected main text.
Expression and innate immune response
| Record | Reported result | Interpretation |
|---|---|---|
| Screen | Single 0.5 mg/kg RNA dose; tissue EGFP at 24 h | Complete reporter-mRNA LNP |
| Liver EGFP | 2.64 in the reported 10E7 pg/g-liver column | MC3 2.07; GVS-18-B6 5.30 in the same column |
| Spleen EGFP | 1.15 in the reported 10E6 pg/g-spleen column | MC3 1.10; GVS-18-B6 0.58 |
| Plasma MCP-1 / CCL2 | 3152 pg/mL | MC3 159; GVS-18-B6 81 pg/mL |
| Confirmatory study | Intravenous EGFP-mRNA LNP; n=3 BALB/c mice/group; liver EGFP at 24 h and MCP-1 at 6 h | Figure 2; figure bars were not digitized |
Holland et al., Table 1 and Figure 2. Scientific-notation column labels are retained as printed. MCP-1 and CCL2 denote the same chemokine.
Dose-dependent tolerability
| Record | Reported result | Interpretation |
|---|---|---|
| Study | BALB/c mice, n=4/group; intravenous nonstimulatory-siRNA LNP; 1, 2, 4 and 6 mg/kg RNA | Distinct from the EGFP-mRNA screen |
| Timing | MCP-1 and IL-6 at 6 h; ALT, AST and body weight at 24 h | Different endpoint collection times |
| Compound 9 findings | Higher-dose groups showed more pronounced inflammatory/liver-enzyme responses and weight loss than the better-tolerated comparators described in the paper | No exact threshold, NOAEL or weight-loss percentage inferred from prose |
| Clearance | Compound 9 caused higher cytokine/enzyme responses despite faster clearance than MC3 | Clearance alone does not establish safety |
| Monkey studies | NHP data in the paper concern GVS-18-B6 | Not A9-specific evidence |
Holland et al., Figure 3 and Discussion. The figure caption flags early termination of moribund animals; exact lipid/dose attribution requires reading the original panel.
Evidence scope
| Record | Reported result | Interpretation |
|---|---|---|
| Clinical platforms | Review articles describe probable lipid classes | Do not present A9 as a verified clinical vaccine ingredient |
| Missing information | Validated human safety, compound-specific NHP data and a unique N/P value | Not established by these records |
| Original figures | 2024 article is CC BY-NC-ND 4.0 | Link to source; do not reproduce its figures commercially without permission |
Primary data and review-level inference are kept separate.
References and source locations
- Du X, Ansell SM. US10221127B2. Lipids and lipid nanoparticle formulations for delivery of nucleic acids. 5 March 2019. Compound 9; Examples 28–30, Table 3.
- Holland R, Lam K, Jeng S, et al. Silicon Ether Ionizable Lipids Enable Potent mRNA Lipid Nanoparticles with Rapid Tissue Clearance. ACS Nano 18(15), 10374–10387 (2024). DOI:10.1021/acsnano.3c09028. Table 1, Figures 2–3. Supporting Information Figure S1 and Compound 9 identity entry.
- Buschmann MD et al. Nanomaterial Delivery Systems for mRNA Vaccines. Vaccines 9(1), 65 (2021). DOI:10.3390/vaccines9010065. Review identity context; reference 59.