Acuitas A9

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.

Total lipid (µmol)

Component	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.