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5A2-SC8
Formulation & Performance
Formulation & Performance
Study-specific compositions, preparation conditions and experimental outcomes for 5A2-SC8.
The archived 2016 article and the complete 2024 SI were reviewed. The 2024 base-recipe and RNA-loading values are retained from the prior page extraction; newly checked SI results are identified by figure.
1. Formulations and component amounts
Reported composition and calculated mass are separate. Molecular-weight inputs use the current catalog values; DMG-PEG2000 is fixed initially at 2507. Edit inputs only when using a verified alternative material.
2024 four-lipid base
molar parts (sum 63)Prior 2024 Methods extraction
| Component | Molecular weight | Molar parts | Normalized mol% | Amount (µmol) | Weight (mg) |
|---|---|---|---|---|---|
| 5A2-SC8 | 23.810 | 25.9034 | 47.7079 | ||
| DOPE | 23.810 | 25.9034 | 19.2729 | ||
| Cholesterol | 47.619 | 51.8069 | 20.0311 | ||
| DMG-PEG2000 | 4.762 | 5.1807 | 12.9880 |
Calculated total: 100.0000 mg lipid. RNA, solvent and process loss are excluded.
2024 C6-mDLNP
mol%Prior 2024 recipe extraction; SI identifies C6
| Component | Molecular weight | Reported molar entry | Calculated mass |
|---|---|---|---|
| 5A2-SC8 | 1841.76 | 19 | Not calculated |
| DOPE | 744.03 | 19 | Not calculated |
| Cholesterol | 386.65 | 38 | Not calculated |
| DMG-PEG2000 | 2507 | 4 | Not calculated |
| Palmitic acid hydrazide (C6) | Not confirmed | 20 | Not calculated |
No complete mass recipe is generated for this formulation while composition or identity-dependent inputs remain unresolved.
5A2-SC8 uses the catalog molecular weight 1841.76.
How component weights are calculated
For total lipid mass M (mg), molar parts rᵢ and molecular weight MWᵢ: component mass = M × rᵢ × MWᵢ / Σ(r × MW). Component amount (µmol) = component mass (mg) × 1000 / MWᵢ. Molar parts are normalized only for the displayed percentage. The calculation does not infer N/P or RNA dose.
2. Preparation and experimental setup
| Parameter | Reported procedure / limitation | Source |
|---|---|---|
| Cargo-specific loading | Earlier Methods extraction: total lipid:RNA mass ratios 40:1 (luciferase), 20:1 (Cre), and 10:1 (Cas9 / base-editor cargo). | 2024 study; these are not N/P ratios |
| Covalent fifth component | C6 is palmitic acid hydrazide; AA11 and SA-NHS are separate tested covalent lipids. Do not label all five-component particles as the same recipe. | 2024 SI Results and Discussion |
| Preparation gaps | Exact phase ratio, buffer, mixing and purification parameters require checking the full 2024 Methods before reproducing a batch. | Not inferred from the SI or the four-lipid ratio |
| Older siRNA platform | The 2016 siRNA work uses a different formulation context. Its lipid recipe and FVII knockdown results are not transferred to the 2024 bone-marrow system. | 2016 article versus 2024 article/SI |
3. Particle characterization
| Measurement / batch | Reported result | Evidence context |
|---|---|---|
| Base composition | 15:15:30:3 is a molar ratio; normalized percentages are calculated only for the mass table | Sum = 63 |
| Five-component identity | 20 mol% covalent lipid is a formulation design variable | 2024 SI Fig. 11 |
| Size / encapsulation | No single batch value is assigned across Luc, Cre, Cas9 and base-editor LNPs | Cargo and fifth-component identity must remain linked |
4. Performance by experiment
| Experiment and dose | Readout and comparator | Result and source |
|---|---|---|
| Covalent-lipid mechanism control SA-NHS formulation versus hydrolyzed stearic acid or an unreactive headgroup analog | Readout: Luciferase organ-imaging assay Comparator: Matched negative-control formulations | Hydrolyzed and unreactive comparators did not confer the same bone-marrow reporter delivery. The reactive component, rather than 5A2-SC8 alone, contributes to tropism.2024 SI Fig. 2; SI Results |
| Ionizable-lipid comparison 20 mol% AA11 in 5A2-SC8-, SM-102- or ALC-0315-based LNP; C57BL/6 IV reporter experiment | Readout: 6 h Comparator: SM-102 and ALC-0315 study formulations | Bone-marrow homing was retained across carrier classes; the 5A2-SC8 formulation gave stronger delivery in this comparison and was used subsequently.2024 SI Fig. 4; dose not transcribed here |
| Covalent-lipid fraction AA11 at 10%, 20% or 30%; Cre mRNA in reporter mice | Readout: SI cell-transfection endpoint Comparator: 10% and 20% AA11 | Raising AA11 from 10% to 20% did not improve all populations; 30% markedly reduced delivery, particularly in stem/progenitor cells.2024 SI Fig. 11 |
| Formulation storage C6-mDLNP with Cre mRNA; stored for 3 days before IV administration | Readout: After the study reporter-expression interval Comparator: Fresh particles; room temperature / −20 °C storage | 4 °C storage maintained measured cell transfection; room temperature and −20 °C reduced activity. Particle-size/PDI results supported this trend.2024 SI Figs. 12–13 |
| Ex vivo sickle-cell editing workflow Townes-mouse CD117+ cells; 10 pg RNA/cell; ABE8e_NRCH mRNA:sgHBB = 2:1 by mass | Readout: 14-day erythroid differentiation; separate 18 h hypoxia assay Comparator: Study differentiation controls | Editing and erythrocyte phenotypes were evaluated in an ex vivo workflow. No in vivo cure percentage is inferred from these methods.2024 SI Methods, printed p.3 |
| Acute tolerability markers C57BL/6J mice; C6-LNP luciferase mRNA 0.6 mg/kg IV | Readout: 24 h and day 7 Comparator: Study controls | Some bone/marrow and complement-related markers changed at 24 h; measured markers returned toward baseline at day 7. This is not evidence of no acute response.2024 SI Figs. 21–23 |
Mechanistic evidence
The SI supports an association between reactive-lipid chemistry and bone-marrow delivery. Protein-corona/ApoE observations do not establish one exclusive receptor mechanism for every formulation.
5. Interpretation and unresolved details
- Bone-marrow performance belongs to the complete five-component formulation, including the reactive lipid. The four-lipid base is not assigned the same targeting claim.
- The four-lipid mass table is available; a complete C6-mDLNP mass table is withheld until every component molecular-weight basis is confirmed.
- The 2016 and 2024 studies differ in cargo, helper lipids and assay goals; results are not pooled.
- A complete preparation protocol still requires the full 2024 Methods.
Results apply to the stated LNP composition, cargo, process, dose, route and model. LNP experimental measurements are not batch-release specifications for the isolated lipid.
6. References and data access
Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells. Nature Nanotechnology (2024). Zhou K et al. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model. PNAS (2016). SI Fig.S26.
DOI: 10.1038/s41565-024-01680-8
Download experiment table (CSV) · Open printable Formulation & Performance guide
Revision FP-20261022 · Source review: 22 October 2026 · DC Chemicals