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503O13
Formulation & Performance
Formulation & Performance
Study-specific compositions, preparation conditions and experimental outcomes for 503O13.
Complete 2014 article and 15-page supporting information rechecked, including visual review of the immune-cell and body-weight figures. Standard screening, optimized Factor VII dose response, and data from other lipidoids are separated.
1. Formulations and component amounts
Reported composition and calculated mass are separate. Molecular-weight inputs use catalog values or an explicitly identified reference average; DMG-PEG2000 is fixed initially at 2507. Edit inputs only when using a verified alternative material.
Standard screening LNP
mol%Main article Results, p.4; Methods, p.8
| Component | Molecular weight | Molar parts | Normalized mol% | Amount (µmol) | Weight (mg) |
|---|---|---|---|---|---|
| 503O13 | 50.000 | 57.5727 | 69.4312 | ||
| Cholesterol | 38.500 | 44.3309 | 17.1406 | ||
| DSPC | 10.000 | 11.5145 | 9.0982 | ||
| DMG-PEG2000 | 1.500 | 1.7272 | 4.3300 |
Calculated total: 100.0000 mg lipid. RNA, solvent and process loss are excluded.
Optimized 503O13 LNP
Optimized ratio not disclosedFig.6d and Results, pp.7–8; general formulation method does not identify the exact optimized 503O13 composition
| Component | Molecular weight | Reported molar entry | Calculated mass |
|---|---|---|---|
| 503O13 | 1205.975 | Not recovered | Not calculated |
| Cholesterol | 386.65 | Not recovered | Not calculated |
| DSPC | 790.15 | Not recovered | Not calculated |
| DMG-PEG2000 | 2507 | Not recovered | Not calculated |
No complete mass recipe is generated for this formulation while composition or identity-dependent inputs remain unresolved.
The paper specifies mPEG2000-DMG molecular weight 2660. The website component calculator uses the catalog convention DMG-PEG2000 = 2507; its calculated masses therefore represent the catalog component, not an exact recreation of that historical PEG grade.
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 |
|---|---|---|
| Organic phase | Lipidoid, cholesterol, DSPC and mPEG2000-DMG were dissolved in 90% ethanol plus 10% 10 mM sodium citrate by volume. | Methods: Formulation of LNPs, p.8 |
| Aqueous phase and loading | siRNA was diluted in 10 mM sodium citrate. Lipidoid:siRNA was 5:1–10:1 by mass depending on the experiment. This is not a total-lipid:siRNA mass ratio; no N/P value is specified. | Methods: Formulation of LNPs, p.8 |
| Mixing | Equal volumes of lipid and siRNA solutions were rapidly mixed by microfluidic device or pipetting. The paper does not assign a specific mixing implementation to each 503O13 experiment. | Methods: Formulation of LNPs, p.8 |
| Buffer exchange | Dilution in PBS followed by dialysis against PBS for 90 min using a 3,500-MWCO cassette. | Methods: Formulation of LNPs, p.8 |
| Optimization boundary | The general series used 50:38.5:(11.5−X):X lipidoid/cholesterol/DSPC/PEG-lipid. The specific X for optimized 503O13 is not supplied. The separately optimized 304O13 PEG fraction cannot be transferred to 503O13. | Methods p.8; Results p.4 and Fig.6d |
| Unreported process details | Buffer pH, precise microfluidic flow settings, final concentration and an experiment-specific 503O13 loading ratio are not reported in the recovered method. A sterile-filtration step is not stated there. | Methods p.8 |
3. Particle characterization
| Measurement / batch | Reported result | Evidence context |
|---|---|---|
| Particle diameter / PDI / encapsulation | No numerical 503O13-specific values recovered. Table 1 describes other individual lipidoids; library ranges are not product-specific specifications. | Main article Table 1 and Fig.6 |
| Apparent particle pKa | The 500-series text places 503O13 among candidates satisfying pKa ≥5.5; no exact 503O13 value is tabulated. | Results p.6 and Fig.6 |
| Tolerability endpoint | 503O13 appears in the 5 mg/kg siRNA body-weight panel; this is a limited body-weight endpoint, not a full toxicology assessment. | Supplementary Fig.9, PDF p.13 |
4. Performance by experiment
| Experiment and dose | Readout and comparator | Result and source |
|---|---|---|
| Initial hepatic Factor VII screen Female C57BL/6 mice ≥6 weeks; anti-FVII siRNA; intravenous tail vein; 5 mg/kg siRNA; injection volume 0.01 mL/g | Readout: 48 h Comparator: PBS / FVII baseline | 503O13 is among the 500-series formulations producing >95% FVII silencing. The exceptions identified by the authors were 509O13 and 510O13. n=3; mean±SD.Fig.6b; Results pp.6–8; In vivo gene silencing, p.9 |
| Unoptimized dose-response ranking 503O13 screening formulation; female C57BL/6 mice; intravenous anti-FVII siRNA | Readout: 48 h Comparator: Other second-generation lipidoids at the screening composition | Nonoptimized 503O13 EC50 is approximately 0.05 mg/kg by the plotted bar; this is an approximate graphical value. It is separate from the optimized 0.01 mg/kg result.Fig.6c, p.7 |
| Optimized Factor VII dose response Optimized 503O13 LNP; intravenous anti-FVII siRNA; doses plotted 5, 0.5, 0.1, 0.03, 0.01 and 0.003 mg/kg | Readout: 48 h Comparator: 503O13 with nontargeting siRNA | Reported EC50 0.01 mg/kg siRNA. The nontargeting control did not suppress FVII. n=3; mean±SD; one-way ANOVA F(6,14)=86.69, P<0.0001; Tukey comparison P<0.05 for each tested active-siRNA dose versus siControl.Fig.6d and caption, p.7; Results p.8 |
| Body-weight screen 500-series LNPs including 503O13; 5 mg/kg siRNA | Readout: Time point not specified in the figure caption Comparator: PBS | No statistically significant body-weight decrease versus PBS by Student’s t-test. The 503O13 group has three plotted animals; no 503O13-specific cytokine, clinical-chemistry or histology conclusion follows from this panel.Supplementary Fig.9, PDF p.13 |
Mechanistic evidence
503O13 is an ester-containing lipidoid selected within a structure–activity framework involving O13 tails, multiple substitution sites, a tertiary amine and sufficient apparent particle pKa. These are library-level predictive associations. Direct 503O13-specific trafficking and endosomal-escape measurements were not recovered.
5. Interpretation and unresolved details
- The 0.01 mg/kg EC50 belongs to the optimized LNP, whose exact composition was not disclosed. The standard 50:38.5:10:1.5 recipe is a screening reference and is not the proven recipe behind that EC50.
- Rapid blood clearance, liver/spleen biodistribution, the six-minute 50% clearance observation, and detailed comparisons with C12-200 were measured for 304O13, not 503O13 (Fig.4; Supplementary Figs.6–7).
- The second-generation immune-cell experiment in Supplementary Fig.8 includes 503O14, not 503O13. It does not establish 503O13 spleen or immune-cell silencing.
- This is a four-component siRNA LNP study. It does not establish that neat 503O13 is a single-component delivery system or demonstrate product-specific mRNA efficacy.
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
Whitehead KA, Dorkin JR, Vegas AJ, et al. Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nature Communications. 2014;5:4277.
Download experiment table (CSV) · Open printable Formulation & Performance guide
Revision FP-20261024-b2 · Source review: 24 October 2026 · DC Chemicals