Table 2
Parameter: Organic and aqueous phases | Reported procedure / limitation: Lipids in ethanol; siRNA approximately 1 mg/mL in 10 mM citrate buffer, pH 4. | Source: Main Methods; retained prior extraction
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L319
Literature records
Search the tables and observations reproduced from the product literature guide. Rows may represent measurements, recipes or experimental context; they are not all independent experiments.
Table 2
Parameter: N/P and mass loading | Reported procedure / limitation: Lipid nitrogen:siRNA phosphate ratio 3, corresponding to approximately 10:1 total lipid:siRNA by mass. The mass ratio includes all four lipids. | Source: Main Methods; fresh primary-indexed text corroborates both bases
Table 2
Parameter: Mixing | Reported procedure / limitation: Spontaneous vesicle formation through a union connector; aqueous siRNA stream 15 mL/min and ethanol lipid stream 5 mL/min. | Source: Main Methods; retained prior extraction
Table 2
Parameter: Buffer exchange | Reported procedure / limitation: Ethanol removal and PBS exchange by dialysis or tangential-flow diafiltration. PBS: 155 mM NaCl, 3 mM Na2HPO4, 1 mM KH2PO4, pH 7.5. | Source: Main Methods; retained prior extraction
Table 2
Parameter: Filtration | Reported procedure / limitation: 0.2 µm sterile filtration after formulation/buffer exchange. | Source: Main Methods; retained prior extraction
Table 2
Parameter: Process interpretation | Reported procedure / limitation: The reported 3:1 aqueous:ethanol flow ratio is a volumetric mixing setting, not N/P or lipid molar composition. | Source: Derived explanation of the reported method
Table 3
Measurement / batch: Apparent LNP pKa | Reported result: 6.38, TNS titration | Evidence context: Main Table1; retained prior extraction
Table 3
Measurement / batch: Particle diameter | Reported result: Approximately 60 nm | Evidence context: Main Results/Methods; retained prior extraction
Table 3
Measurement / batch: siRNA entrapment | Reported result: Greater than 90% | Evidence context: Main Results/Methods; retained prior extraction
Table 3
Measurement / batch: Mouse FVII ED50 | Reported result: Less than 0.01 mg/kg siRNA | Evidence context: Main Table1/Fig.2; 48 h hepatic Factor VII protein endpoint; not a human dose
Table 4
Experiment and dose: Mouse Factor VII silencing C57BL/6 mice; intravenous anti-FVII siRNA at 0.01, 0.03 and 0.1 mg/kg; n=3 | Readout and comparator: Readout: 48 h Comparator: Baseline/control-siRNA and lipid comparisons in the primary study | Result and source: Approximately 75% FVII silencing at 0.01 mg/kg; reported ED50 below 0.01 mg/kg. Main Table1 and Fig.2; retained prior extraction
Table 4
Experiment and dose: Mouse plasma lipid pharmacokinetics L319 LNP at 0.3 mg/kg siRNA intravenously; n=2 per time point | Readout and comparator: Readout: 0–8 h Comparator: Time-zero/early postdose levels | Result and source: 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
Table 4
Experiment and dose: Mouse liver lipid and metabolite kinetics L319 LNP at 0.3 mg/kg siRNA intravenously; n=2 per time point | Readout and comparator: Readout: Up to 48 h Comparator: Early postdose liver levels | Result and source: 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
Table 4
Experiment and dose: Rat radiolabel elimination Radiolabeled-lipid LNP study in rats; n=4; exact administered dose not recovered in this pass | Readout and comparator: Readout: 24–72 h Comparator: Injected radiolabel balance | Result and source: 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
Table 4
Experiment and dose: Rat tolerability Sprague-Dawley rats; single intravenous siRNA-LNP doses 1, 3, 5 or 10 mg/kg; n=5 per group | Readout and comparator: Readout: Study-specific clinical chemistry and tolerability observations Comparator: L343 comparator and study controls | Result and source: 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
Table 4
Experiment and dose: Monkey hepatic TTR silencing Cynomolgus monkeys; anti-TTR siRNA 0.3 mg/kg; 15-minute intravenous infusion; n=3 | Readout and comparator: Readout: 48 h liver biopsy Comparator: Control treatment in the primary study | Result and source: Approximately 70% hepatic TTR mRNA silencing. Main Results, Fig.6; retained prior extraction