Formulation & Performance
Updated against the author-hosted 2026 Cell article, including its STAR Methods and supplementary figures. The final article uses a 30:39:30:1 DOTAP-containing pulmonary formulation; this replaces the earlier preprint formulation in this evidence module.
LUMI6, LUMI-6 and DC60793 refer to the same catalog lipid here. LUMI-6D and LUMI-6Cl are separate comparator compounds. The 20.3% result is reporter activation in an Ai9 model, not a disease-correction percentage.
Formulation components and molecular-weight conversion
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| LUMI6 | DC60793 | 822.07 | 30 | 0.246621 |
| DOTAP | Not uniquely mapped | Not established | 39 | Not calculable from disclosed data |
| Cholesterol | DCD-041 | 386.65 | 30 | 0.115995 |
| DMG-PEG2000 | DC40169 | 2507 | 1 | 0.025070 |
Final article STAR Methods: ionizable lipid / DOTAP / cholesterol / DMG-PEG2000 = 30:39:30:1 mol% for intratracheal experiments unless otherwise stated. DMG-PEG2000 MW is 2507. DOTAP counterion/catalog identity is not sufficiently specified for an exact mass assignment and remains blank. Neither N/P nor total lipid:RNA mass ratio is assigned.
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 % |
|---|---|---|---|---|
| LUMI6 | ||||
| DOTAP | ||||
| Cholesterol | ||||
| DMG-PEG2000 |
Matched DOPE-containing formulation comparison
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| LUMI6 | DC60793 | 822.07 | 35 | 0.287724 |
| DOPE | DC33634 | 744.03 | 16 | 0.119045 |
| Cholesterol | DCD-041 | 386.65 | 46.5 | 0.179792 |
| DMG-PEG2000 | DC40169 | 2507 | 2.5 | 0.062675 |
Final STAR Methods and supplementary formulation comparison: 35:16:46.5:2.5 mol%. This is separated from the automated-screen paragraph, which uses a phosphoethanolamine-based C14-PEG description.
Component mass calculator
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 % |
|---|---|---|---|---|
| LUMI6 | ||||
| DOPE | ||||
| Cholesterol | ||||
| DMG-PEG2000 |
DSPC-containing comparison / intramuscular safety formulation
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| LUMI6 | DC60793 | 822.07 | 50 | 0.411035 |
| DSPC | DC57005 | 790.15 | 10 | 0.079015 |
| Cholesterol | DCD-041 | 386.65 | 38.5 | 0.148860 |
| DMG-PEG2000 | DC40169 | 2507 | 1.5 | 0.037605 |
Final STAR Methods: DSPC-containing formulation 50:10:38.5:1.5. The intramuscular tolerability experiment excludes DOTAP. Route-specific safety findings are not transferred to the DOTAP formulation.
Component mass calculator
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 % |
|---|---|---|---|---|
| LUMI6 | ||||
| DSPC | ||||
| Cholesterol | ||||
| DMG-PEG2000 |
Final-publication formulation and comparison context
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Version | Cell 2026 article, DOI 10.1016/j.cell.2026.01.012; author-hosted article-in-press PDF includes supplementary figures | Published record: Cell 189, 1620–1635.e25 |
| Pulmonary candidate LNP | LUMI6 / DOTAP / cholesterol / DMG-PEG2000 = 30:39:30:1 | STAR Methods; supersedes the old preprint ratio in this module |
| Comparator context | SM-102 and MC3 reference LNPs use DSPC 50:10:38.5:1.5 unless otherwise stated | Some comparisons change helper lipid and ratio as well as the ionizable lipid |
| Unresolved inputs | No N/P or total lipid:RNA mass ratio assigned; DOTAP salt MW not assigned | RNA:RNA ratios below are cargo ratios only |
| Size/PDI | Main Fig. 5c–d reports DLS measurements for the six candidates | Exact values are not inferred from graph heights; no batch release specification |
Cellular expression and endosomal escape
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Matched lipid comparison | LUMI6 versus LUMI-6D in HBE cells; 18 h; 1.8-fold higher luciferase expression reported | Main Results and Fig. S2b; matched formulation conditions |
| Cell viability | CCK-8 assays did not show a significant difference between brominated and debrominated candidates | Fig. S2c; does not establish absence of toxicity at all concentrations |
| Intracellular RNA | At 2–6 h both formulations showed endosomal localization; at 18 h LUMI6 showed more cytoplasmic RNA signal | Fig. S2d–e; fluorescence-based mechanistic evidence |
| Formulation sensitivity | Supplementary comparison examines DOPE, DSPC and DOTAP helper systems | Fig. S4f–g; helper system influences measured potency |
Pulmonary expression and Ai9 reporter editing
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Luciferase screen | Intratracheal Fluc mRNA 0.25 mg/kg; readout at 6 h; n = 3 | STAR Methods and Fig. 5; use final-publication dose context |
| Ai9 schedule | Intratracheal dosing on days 0, 3 and 6; analysis day 9 | Main Fig. 6a and STAR Methods |
| Cargo dose | Cas9 mRNA 1 mg/kg per administration; Cas9 mRNA:sgRNA 4:1 by mass | Dose is explicitly stated on the Cas9 mRNA basis |
| Epithelial cells | EpCAM-positive population: 20.3% tdTomato-positive with LUMI6 versus 15.4% with SM-102 | Fig. 6c; n = 3 independent animals, two samples per mouse |
| Endothelial cells | CD31-positive population: 1.8% versus 2.7% with SM-102 | Fig. 6c; separate cell population |
| Airway localization | Reporter fluorescence colocalized with club and ciliated cell markers | Fig. 6d; no cell-type percentage is assigned from microscopy |
The Fig. 6b caption describes a 6-hour Fluc experiment within the Ai9 editing figure. That panel is not used here to derive an editing percentage or resolve the dosing schedule; Fig. 6a/c and STAR Methods support the reporter record.
Additional base-editing reporter evidence
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Model | LumA luciferase reporter mice with an inactivating reporter mutation | Fig. S5; reporter restoration is distinct from the Ai9 deletion assay |
| Study schedule | Intratracheal 0.75 mg/kg per dose on days 0 and 7; analysis day 11 | Fig. S5b; ABE mRNA:guide RNA 1:1 mass ratio in STAR Methods |
| Result | Higher lung luminescence and sequencing-detected base conversion with LUMI6 than SM-102 | Fig. S5c–f; no exact percentage is inferred from bars |
| Interpretation | Functional reporter restoration with sequencing support | Not correction of a patient disease allele or clinical efficacy |
Repeat-dose tolerability and immune response
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Intratracheal study | Five 0.5 mg/kg mRNA-LNP administrations on days 0, 7, 14, 21 and 28; 6/24 h after the final dose assessed | Fig. S6a; DSPC and DOTAP LUMI6 groups are distinct |
| Measured endpoints | Cytokine/chemokine panels, major-organ histology, hemolysis and complement sC5b-9 | Fig. S6; cytokine panels n = 3, hemolysis/complement n = 5 |
| Inflammatory interpretation | The authors report tolerability comparable to SM-102; plots show treatment-related cytokine/complement signals | Comparable to a benchmark does not mean no immune activation |
| Intramuscular study | Five weekly 0.5 mg/kg doses; DOTAP excluded; cytokines and histology assessed | Fig. S7; 6/24 h sampling and n = 3 |
| Scope | No significant histological abnormalities reported under tested conditions | Route-, formulation- and dose-specific rodent evidence; no human safety conclusion |
Original study figures
Main Figs. 5–6: lung expression, reporter flow cytometry and airway microscopy — Original source figures.
Supplementary Figs. S2, S5–S7: cellular mechanism, base-editing reporter and repeat-dose safety — Original source figures.