Formulation & Performance
1A7B13 is the permanently charged lung-targeting component of a five-lipid formulation. Results are separated by reporter, cell population and assay; the high Cre reporter percentages are not presented as endogenous genome-editing rates.
The catalog uses the 1:1 bromide salt identity, C65H130BrNO4, molecular weight 1069.66. This is a catalog calculation basis, not a batch counterion assay. The ionizable companion lipid in the cited LNP is 4A3-SC7, not 4A3-SC8.
Formulation components and molecular-weight conversion
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| 4A3-SC7 | DC60855 | 1411.07 | 11.9 | 0.167917 |
| DOPE | DC33634 | 744.03 | 11.9 | 0.088540 |
| Cholesterol | DCD-041 | 386.65 | 23.82 | 0.092100 |
| DMG-PEG2000 | DC40169 | 2507 | 2.38 | 0.059667 |
| Lipid 1A7B13 | DC68023 | 1069.66 | 50 | 0.534830 |
Component order: 4A3-SC7/DOPE/cholesterol/DMG-PEG2000/1A7B13 = 11.90:11.90:23.82:2.38:50 mol%. The reported total lipid:mRNA mass ratio is 40:1. This is not 1A7B13:mRNA or N/P. The conversion uses the bromide-salt MW for 1A7B13 and 2507 for DMG-PEG2000.
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 % |
|---|---|---|---|---|
| 4A3-SC7 | ||||
| DOPE | ||||
| Cholesterol | ||||
| DMG-PEG2000 | ||||
| Lipid 1A7B13 |
Formulation role and particle evidence
| Study / condition | Result | Interpretation |
|---|---|---|
| LuT component | Permanently cationic, at 50 mol% of the five-component LNP | Complements the ionizable 4A3-SC7 component; not a one-component carrier. |
| Particle-size screen | Library particles were predominantly approximately 100–150 nm with PDI <0.2 | Library-level range, not a lot specification for 1A7B13. |
| Mechanistic assays | Enhanced fusion/release in endosomal-mimic assays and altered protein-corona profiles | Mechanistic associations; not an in vivo escape percentage. |
Main Figs. 2–5, Methods and Supplementary Fig. 18. Product conversion reflects the approved bromide salt.
Lung expression and cellular reporter delivery
| Study / condition | Result | Interpretation |
|---|---|---|
| Luciferase comparisons | 1A7B13 LNPs outperformed DOTAP LNPs across the tested dose-response series | Use source curves rather than assigning the maximum library fold-change to this molecule. |
| Cre reporter; Ai14 mice; 0.3 mg mRNA/kg IV; 48 h | 93.7% pulmonary endothelial and 54.8% epithelial cells reporter-positive | Percent of each gated population; not percent of all lung cells. |
| Lower-dose Cre experiment | Approximately 49.57% epithelial reporter positivity at 0.05 mg/kg | A separate dose experiment; not a genome-editing percentage. |
Main Fig. 4 and Supplementary Figs. 27–31. Cre-dependent recombination and Cas9 editing are different assays.
Cas9 reporter editing: distinct from Cre delivery
| Study / condition | Result | Interpretation |
|---|---|---|
| Ai14 reporter study; two IV doses, 48 h apart; 0.75 mg total RNA/kg per dose | 26.5% reporter-positive total lung cells with 1A7B13 versus 6.2% with DOTAP | Assessed 10 days after the second dose. |
| Cell-type analysis | Approximately 73% endothelial, 34% epithelial and 16% immune cells | Corresponding DOTAP values were approximately 31%, 23% and 6%. |
| Interpretation | Fluorescent reporter activation demonstrates editing in this engineered locus | Does not establish equivalent editing at every endogenous target. |
Main Fig. 6b–e.
Endogenous-target assay and interpretation
| Study / condition | Result | Interpretation |
|---|---|---|
| PTEN locus, total-lung DNA | 20.23% indels with 1A7B13 versus 2.20% with DOTAP | Sequencing-derived endpoint; not the Cre reporter percentage. |
| Study context | Two 0.75 mg total RNA/kg IV doses; post-treatment genomic analysis | Preclinical proof of delivery/editing, not a therapeutic recommendation. |
| Immunostaining | Loss of protein staining was measured separately | Protein-negative cells and DNA indels are not interchangeable measures. |
Main Fig. 6f–i. The study text and timeline should be consulted for the endpoint-specific assessment schedule.
Acute tolerability and translational limits
| Study / condition | Result | Interpretation |
|---|---|---|
| Luciferase mRNA LNP; 0.75 mg/kg IV; C57BL/6 mice; n = 3 | No overt lung histological injury in the reported 48 h assessment | Acute study with PBS and inflammatory positive controls. |
| Thrombosis comparison | No observable clots in the tested 1A7B13-LNP group; DOTAP lipoplex control showed clots | The control is a lipoplex formulation, not every possible DOTAP LNP. |
| Serum chemistry | ALT, AST, BUN and creatinine assessed at 24 and 48 h in supplementary studies | No overt acute signal reported under those conditions. |
| Remaining evidence needs | Repeat-dose tolerability, durability and larger-animal translation | Not established by the reported acute mouse results. |
Main Fig. 5i–j and Supplementary Figs. 37–39.
Original study figures
Lung expression and cell-type delivery — Figure 4 — Original source figures.
Mechanistic and acute tolerability data — Figure 5 — Original source figures.
Reporter and endogenous editing results — Figure 6 — Original source figures.