Formulation & Performance
The Dual SORT study uses distinct liver and lung carriers. The original lung carrier contains 5A2-SC8 and DOTAP; an updated lung carrier contains 4A3-SC7 and DORI. Results of the combined treatment are not treated as properties of 4A3-SC7 alone.
DC60855 is 4A3-SC7, not 4A3-SC8. Source nomenclature distinguishes 4A3-Cit, the additional liver SORT lipid, from the base ionizable lipid.
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 | 15.04 | 0.212225 |
| DOPE | DC33634 | 744.03 | 23.04 | 0.171425 |
| Cholesterol | DCD-041 | 386.65 | 38.72 | 0.149711 |
| DMG-PEG2000 | DC40169 | 2507 | 3.2 | 0.080224 |
| 4A3-Cit (Cit Liver SORT lipid) | Not uniquely mapped | Not established | 20 | Not calculable from disclosed data |
Lead ABE liver formulation #12, Supplementary Table 3 (printed p.28; PDF p.29): 15.04:23.04:38.72:3.2:20 mol%; total lipid:RNA = 20:1 by mass. 4A3-Cit has not been uniquely mapped to a catalog product/MW, so its mass and the total mass percentage remain unassigned. N/P is not inferred.
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 % |
|---|---|---|---|---|
| 4A3-SC7 | ||||
| DOPE | ||||
| Cholesterol | ||||
| DMG-PEG2000 | ||||
| 4A3-Cit (Cit Liver SORT lipid) |
Earlier liver reporter formulation — Supplementary Fig. 1
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| 4A3-SC7 | DC60855 | 1411.07 | 19.04 | 0.268668 |
| DOPE | DC33634 | 744.03 | 19.04 | 0.141663 |
| Cholesterol | DCD-041 | 386.65 | 38.72 | 0.149711 |
| DMG-PEG2000 | DC40169 | 2507 | 3.2 | 0.080224 |
| 4A3-Cit | Not uniquely mapped | Not established | 20 | Not calculable from disclosed data |
Luciferase formulation from Supplementary Fig. 1. Its composition and particle measurements are kept separate from the optimized ABE formulation.
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 % |
|---|---|---|---|---|
| 4A3-SC7 | ||||
| DOPE | ||||
| Cholesterol | ||||
| DMG-PEG2000 | ||||
| 4A3-Cit |
Updated pulmonary formulation — Supplementary Fig. 11
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| 4A3-SC7 | DC60855 | 1411.07 | 21.6 | 0.304791 |
| DOPE | DC33634 | 744.03 | 12 | 0.089284 |
| Cholesterol | DCD-041 | 386.65 | 24.4 | 0.094343 |
| DMG-PEG2000 | DC40169 | 2507 | 2 | 0.050140 |
| DORI | Not uniquely mapped | Not established | 40 | Not calculable from disclosed data |
4A3-SC7 / DOPE / cholesterol / DMG-PEG2000 / DORI = 21.6:12:24.4:2:40 mol%. DORI is a distinct SORT lipid; DOTAP values and the original 5A2-SC8 formulation are not substituted.
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 % |
|---|---|---|---|---|
| 4A3-SC7 | ||||
| DOPE | ||||
| Cholesterol | ||||
| DMG-PEG2000 | ||||
| DORI |
Cargo-specific liver formulation optimization
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| ABE formulation #1 | 19.04:19.04:38.72:3.2:20; lipid:RNA 20:1; EE 58 ± 3%; size 130 ± 41 nm; PDI 0.28 ± 0.03 | Supplementary Table 3; values as reported |
| ABE formulation #12 | 15.04:23.04:38.72:3.2:20; lipid:RNA 20:1; EE 87 ± 5%; size 74 ± 4 nm; PDI 0.17 ± 0.02 | Supplementary Table 3; lead formulation |
| Cargo-length comparison | sgRNA: EE 91 ± 3%, 71 ± 5 nm; Cre mRNA: 89 ± 2%, 81 ± 4 nm; ABE mRNA: 48 ± 10%, 98 ± 20 nm | Supplementary Table 2; a separate cargo comparison, not formulation #12 release values |
| N/P | Not assigned from the available evidence | 20:1 is a total-lipid:RNA mass ratio |
Liver luciferase delivery
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Model and measurement | C57BL/6J mice; IV luciferase mRNA 0.015 mg/kg; 6 h; n = 2 biological replicates | Supplementary Fig. 1 |
| Five-component result | 1.8-fold higher potency than the four-component Cit formulation | Supplementary Fig. 1c; the comparator omits 4A3-SC7 |
| Five-component particles | 71 ± 0.25 nm; PDI 0.16 ± 0.007 | Supplementary Fig. 1a; composition shown separately above |
| Cit-only comparator | 59.6 ± 0.8 nm; PDI 0.18 ± 0.004 | Comparator composition and outcome are not assigned to DC60855 |
Pulmonary delivery with the updated DORI formulation
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Reporter study | Ai14 mice; Cre mRNA 0.3 mg/kg; lung analysis at 2 days; n = 3 | Supplementary Fig. 11 |
| Measured particles | 69 ± 0.7 nm; PDI 0.12 ± 0.009; zeta potential 8.4 ± 0.76 mV | Supplementary Fig. 11a |
| Cell populations | tdTomato-positive endothelial, non-AT2 epithelial, AT2 and immune populations are plotted | Supplementary Fig. 11b; no exact percentage is inferred from bar heights |
| Endpoint meaning | Cre reporter activation documents functional delivery | Not the same endpoint as AATD mutation correction |
Dual-organ base-editing evidence
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Published overall result | Abstract reports 40% liver-cell and 10% lung-AT2 correction, with liver editing maintained for 32 weeks | Article abstract; combined Dual SORT treatment context |
| Functional outcomes | Abstract reports >80% lower Z-A1AT and 89% neutrophil-elastase inhibition in lung lavage fluid | Regimen-level outcomes, not standalone lipid specifications |
| Original dual system | 4A3-SC7/Cit liver LNPs were paired with 5A2-SC8/DOTAP lung LNPs | Supplementary Methods and Fig. S13 identify different ionizable lipids |
| Updated dual system | PiZ mice received 4A3-SC7/Cit liver and 4A3-SC7/DORI lung carriers; 1.5 mg/kg each; analysis day 6; n = 3 | Supplementary Fig. 12; its outcomes are not conflated with the original treatment |
The complete publisher main text was access-restricted during this review. Overall outcome claims above are limited to the published abstract; accessible SI tables and captions were independently checked.
Tolerability and evidence limits
| Study / parameter | Reported evidence | Source / interpretation |
|---|---|---|
| Original dual regimen | Organ H&E and blood biochemistry assessed in C57BL/6J and PiZ mice, n = 3 | Supplementary Fig. 13; includes the 5A2-SC8 lung carrier |
| Updated dual regimen | 1.5 mg/kg Cre mRNA in each carrier; simultaneous IV treatment; 48 h analysis | Supplementary Fig. 14 |
| Safety readouts | Heart, lung, liver, spleen and kidney histology; AST, ALT, BUN and creatinine | Supplementary Fig. 14 reports no signs of inflammation under those conditions |
| Limits | Reporter-cargo tolerability does not establish every editor-cargo regimen or human safety | No NOAEL or clinical safety claim is assigned |
Original study figures
Original main Figs. 1–3: organ-selective delivery and base-editing outcomes — Original source figures.
Supplementary Figs. 1, 11–14 and Tables 1–3: formulations, cells and tolerability — Original source figures.