DLin-MC3-DMA
Recommended because it shares a closely related research category or delivery context. Formulation and performance are product- and study-specific.
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Components are supplied separately; this is not a premixed LNP. RNA/cargo, buffer and formulation service are not included.
L319 (LIPID 319) is a novel ionizable, biodegradable lipid for delivery of short interfering RNAs (siRNAs). L319-LPN displays rapid elimination with pKa of 6.38 and also shows well tolerated up to 10 mg/kg.
| CAS No. | 1351586-50-9 |
| Chemical Name | L319 |
| Synonyms | di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate;bis[(Z)-non-2-enyl] 9-[4-(dimethylamino)butanoyloxy]heptadecanedioate;L319;starbld0004010;DA-64994;DGNMJYUPWDTKJB-ZDSKVHJSSA-N;LIPID L319?;EX-A5248;G16737;1351586-50-9;CS-0188740;MS-31081;GLXC-25938;LIPID L319;BP-28064;HY-139298;SCHEMBL517530;L-319, L 319 , Lipid 319, lipid-319 |
| SMILES | O(C(CCCN(C)C)=O)C(CCCCCCCC(=O)OC/C=C\CCCCCC)CCCCCCCC(=O)OC/C=C\CCCCCC |
| Formula | C41H75NO6 |
| M.Wt | 678.037313699722 |
| Purity | >95% by ELSD-HPLC |
| Storage | Pure form: −20 °C, 1 year; In solvent: −80 °C, 6 months; −20 °C, 1 month. Sealed and protected from light. |
| Shipping condition | Ships from Shanghai. Pure lipid is stable during ice-pack transport. |
| Publication | Maier MA, et al. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics. Molecular Therapy. 2013;21(8):1570-1578. |
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.
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.
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.
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.
| 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 |
| 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 |
| 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 |
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.
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.
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
The product molecular weight is prefilled when available and remains editable. Confirm solvent compatibility and solubility before preparation.
Lipid component weights only. PEG-DMG is represented by the website-standard editable MW 2507. RNA, buffer, solvent, process loss, N/P and the approximately 10:1 total lipid:siRNA ratio are not included in the lipid-component total.
Solvent volumes update from the molecular weight above.
| Mass | 1 mM | 5 mM | 10 mM |
|---|---|---|---|
| 10 mg | 14.7485 mL | 2.9497 mL | 1.4748 mL |
| 25 mg | 36.8711 mL | 7.3742 mL | 3.6871 mL |
| 50 mg | 73.7423 mL | 14.7485 mL | 7.3742 mL |
| 100 mg | 147.4845 mL | 29.4969 mL | 14.7485 mL |
| 250 mg | 368.7113 mL | 73.7423 mL | 36.8711 mL |
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