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L319
Formulation & Performance
Formulation & Performance
Study-specific compositions, preparation conditions and experimental outcomes for L319.
Previously reviewed main-article evidence is retained from the existing live-page record and reorganized by species and assay. Primary search text freshly corroborates N/P 3 and approximately 10:1 total lipid:siRNA loading. Main PDF/SI retrieval was blocked, so the present update does not claim a new complete primary or SI re-review.
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 uses 2507. Edit inputs only when using a verified alternative material.
L319 four-component siRNA LNP
mol%Main Materials and Methods, LNP formulation; previously reviewed record retained
| Component | Molecular weight | Molar parts | Normalized mol% | Amount (µmol) | Weight (mg) |
|---|---|---|---|---|---|
| L319 | 55.000 | 85.9010 | 58.2441 | ||
| DSPC | 10.000 | 15.6184 | 12.3409 | ||
| Cholesterol | 32.500 | 50.7597 | 19.6262 | ||
| DMG-PEG2000 | 2.500 | 3.9046 | 9.7888 |
Calculated total: 100.0000 mg lipid. RNA, solvent and process loss are excluded.
DMG-PEG2000 uses 2507 for component calculations. L319 uses the existing catalog molecular-weight value of 678.037313699722; its structure and salt-form basis have not been independently reverified in this review.
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 and aqueous phases | Lipids in ethanol; siRNA approximately 1 mg/mL in 10 mM citrate buffer, pH 4. | Main Methods; retained prior extraction |
| N/P and mass loading | Lipid nitrogen:siRNA phosphate ratio 3, corresponding to approximately 10:1 total lipid:siRNA by mass. The mass ratio includes all four lipids. | Main Methods; fresh primary-indexed text corroborates both bases |
| Mixing | Spontaneous vesicle formation through a union connector; aqueous siRNA stream 15 mL/min and ethanol lipid stream 5 mL/min. | Main Methods; retained prior extraction |
| Buffer exchange | Ethanol removal and PBS exchange by dialysis or tangential-flow diafiltration. PBS: 155 mM NaCl, 3 mM Na2HPO4, 1 mM KH2PO4, pH 7.5. | Main Methods; retained prior extraction |
| Filtration | 0.2 µm sterile filtration after formulation/buffer exchange. | Main Methods; retained prior extraction |
| Process interpretation | The reported 3:1 aqueous:ethanol flow ratio is a volumetric mixing setting, not N/P or lipid molar composition. | Derived explanation of the reported method |
3. Particle characterization
| Measurement / batch | Reported result | Evidence context |
|---|---|---|
| Apparent LNP pKa | 6.38, TNS titration | Main Table1; retained prior extraction |
| Particle diameter | Approximately 60 nm | Main Results/Methods; retained prior extraction |
| siRNA entrapment | Greater than 90% | Main Results/Methods; retained prior extraction |
| Mouse FVII ED50 | Less than 0.01 mg/kg siRNA | Main Table1/Fig.2; 48 h hepatic Factor VII protein endpoint; not a human dose |
4. Performance by experiment
| Experiment and dose | Readout and comparator | Result and source |
|---|---|---|
| Mouse Factor VII silencing C57BL/6 mice; intravenous anti-FVII siRNA at 0.01, 0.03 and 0.1 mg/kg; n=3 | Readout: 48 h Comparator: Baseline/control-siRNA and lipid comparisons in the primary study | Approximately 75% FVII silencing at 0.01 mg/kg; reported ED50 below 0.01 mg/kg.Main Table1 and Fig.2; retained prior extraction |
| Mouse plasma lipid pharmacokinetics L319 LNP at 0.3 mg/kg siRNA intravenously; n=2 per time point | Readout: 0–8 h Comparator: Time-zero/early postdose levels | Plasma L319 decreased more than 1,000-fold in 4 h; below the 0.8 pmol/mL quantitation limit by 8 h. Estimated plasma half-life under 30 min.Main Results, Fig.3; retained prior extraction |
| Mouse liver lipid and metabolite kinetics L319 LNP at 0.3 mg/kg siRNA intravenously; n=2 per time point | Readout: Up to 48 h Comparator: Early postdose liver levels | Liver L319 decreased approximately 1,000-fold by 24 h and fell below quantitation by 48 h. Monoacid and diacid metabolites were detected and rapidly eliminated.Main Results, Fig.3; retained prior extraction |
| Rat radiolabel elimination Radiolabeled-lipid LNP study in rats; n=4; exact administered dose not recovered in this pass | Readout: 24–72 h Comparator: Injected radiolabel balance | Nearly the entire injected radiolabel was eliminated by 72 h, predominantly during the first 24 h through urine and feces. This is radiolabel recovery and does not prove excretion entirely as unchanged L319.Main Results, Fig.4; retained prior extraction |
| Rat tolerability Sprague-Dawley rats; single intravenous siRNA-LNP doses 1, 3, 5 or 10 mg/kg; n=5 per group | Readout: Study-specific clinical chemistry and tolerability observations Comparator: L343 comparator and study controls | L319 LNP was reported well tolerated through 10 mg/kg siRNA under the tested conditions. The 10 mg/kg figure refers to siRNA cargo dose and is not a general safe dose for neat L319.Main Results, Fig.5; retained prior extraction |
| Monkey hepatic TTR silencing Cynomolgus monkeys; anti-TTR siRNA 0.3 mg/kg; 15-minute intravenous infusion; n=3 | Readout: 48 h liver biopsy Comparator: Control treatment in the primary study | Approximately 70% hepatic TTR mRNA silencing.Main Results, Fig.6; retained prior extraction |
Mechanistic evidence
L319 was developed as a biodegradable ionizable lipid. Ester-containing hydrophobic portions support conversion to monoacid and diacid metabolites, consistent with the observed rapid parent-lipid disappearance and radiolabel elimination. Lipid clearance and pharmacodynamic siRNA silencing are different endpoints; rapid carrier clearance does not imply an equally short silencing effect.
5. Interpretation and unresolved details
- N/P 3 and approximately 10:1 total lipid:siRNA describe different loading bases. Neither is a 10:1 L319-only mass ratio.
- Particle pKa, diameter and entrapment apply to the studied LNP, not the isolated chemical.
- Mouse Factor VII ED50, mouse lipid kinetics, rat elimination, rat tolerability and monkey TTR knockdown remain separate experiments.
- Rat radiolabel recovery measures label-derived material and metabolites; avoid presenting it as unchanged parent-lipid clearance.
- The reported rat tolerability ceiling is siRNA mg/kg under a single-study protocol, not a clinical dose or product safety specification.
- These data support a hepatic siRNA delivery reference formulation; the 2013 study does not by itself establish mRNA, in vivo CAR-T or T-cell engager performance.
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
Maier MA, et al. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics. Mol Ther. 2013;21(8):1570–1578.
Download experiment table (CSV) · Open printable Formulation & Performance guide
Revision FP-20261024-b3 · Source review: 24 October 2026 · DC Chemicals