LP-01 · Formulation & Performance

Literature evidence · DC31000

Formulation & Performance

The 2018 Cell Reports paper reports durable Ttr editing after transient exposure to LP-01-containing LNPs. Serum protein reduction, whole-liver DNA editing and lipid clearance are reported separately.

The paper names the lipid LP01 and the complete formulation LNP-INT01. DC31000 is the lipid component, not a preformulated editor product.

Formulation components and molecular-weight conversion

Component	DC Chemicals product	Molecular weight	Molar ratio	Mass at 1 µmol total lipid (mg)
LP-01	DC31000	852.292	45	0.383531
DSPC	DC57005	790.15	9	0.071113
Cholesterol	DCD-041	386.65	44	0.170126
DMG-PEG2000	DC40169	2507	2	0.050140

Experimental Procedures, LNP Formulation: LP01 / DSPC / cholesterol / PEG2k-DMG = 45:9:44:2 mol%. Reported N/P = 4.5; mRNA:sgRNA = 1:1 by mass. These are different quantities. DMG-PEG2000 uses MW 2507 for the calculated component masses.

Component mass calculator

Prefilled proportions follow the source specified above. Molecular weights and ratios are editable. Results are calculated, not measured study data. No N/P or RNA dose is inferred.

Total lipid (µmol)

Component	Mass (mg)	Mass %
LP-01	—	—
DSPC	—	—
Cholesterol	—	—
DMG-PEG2000	—	—

Formulation and physical properties

Study / parameter	Reported evidence	Source / interpretation
Composition	45% LP01, 9% DSPC, 44% cholesterol, 2% PEG2k-DMG	Main-text Experimental Procedures
Charge/cargo ratios	N/P 4.5; Cas9 mRNA:sgRNA 1:1 mass ratio	N/P is amine-to-RNA-phosphate, not lipid:RNA mass ratio
Particle size and RNA association	Main text reports formulations <100 nm and >95% encapsulation	The underlying SI Table S1 was not independently retrieved; no narrower values assigned
Ionization	Approximate pKa 6.1 reported for LP01	Results section; assay context should accompany comparisons

Cellular delivery and in vitro/in vivo relationship

Study / parameter	Reported evidence	Source / interpretation
Cell model	Mouse primary hepatocytes; transfection assessed at 42–48 h by sequencing	Experimental Procedures, LNP Delivery In Vitro
Guide screening	In vitro guide activity correlated with the corresponding mouse-liver screen	Main Fig. 1c; guide selection affects the delivered system
Co-delivery	Main text reports coformulation more effective than split delivery	SI Fig. S1 referred to by the main text; individual SI panels not rechecked
Interpretation	Results depend on lipid, formulation and RNA design together	The activity is not an intrinsic potency value of the pure lipid

Mouse liver editing and durability

Study / parameter	Reported evidence	Source / interpretation
Long-term study	CD-1 mice; single systemic dose 0.3, 1 or 3 mg/kg RNA; followed up to 12 months	Main Fig. 2f–h; n = 5 at indicated collection points
Highest-dose result	At 3 mg/kg, >97% serum TTR reduction and approximately 70% whole-liver DNA editing	Main Results and Fig. 2; protein knockdown is not editing percentage
Durability	Editing and protein reduction remained stable through the reported 12-month follow-up	Not persistence of intact LNP or Cas9 mRNA
Repeated administration	Multiple doses produced cumulative editing in the reported study	Main Fig. 3; do not substitute a multi-dose result for the single-dose result

Rat response and component clearance

Study / parameter	Reported evidence	Source / interpretation
Rat efficacy	Systemic 1, 2 or 5 mg/kg; dose-dependent response with approximately 70% liver editing and >90% TTR reduction at high response	Main Fig. 4; outcomes depend on guide and dose
RNA clearance	Cas9 mRNA and guide RNA were undetectable in plasma/liver by 72 h in the reported assay	Main Fig. 2a–b; assay detection limit applies
Lipid turnover	Reported LP01 liver half-life approximately 6 h	Main Fig. 2c
Editing kinetics	Editing reached its maximum later, around 96 h	Main Fig. 2d–e; pharmacokinetics and pharmacodynamics are separate

Tolerability and scope

Study / parameter	Reported evidence	Source / interpretation
Reported endpoints	Main text describes mouse/rat tolerability with respect to cytokine responses and body-weight change	Detailed supporting panels S2c–h were not independently rechecked
Tissue selectivity	Liver was the principal delivery site, with low detectable editing also reported in spleen and kidney	Main Discussion and Fig. 4c; liver-directed does not mean exclusive
Study boundary	Rodent preclinical evidence; no human efficacy or universal safety claim	Specific cargo, dose and assay conditions matter
Open items	Complete original SI and panel-level formulation characterization remain to be verified	Do not infer exact PDI, NOAEL or shelf life

Original study figures

Original Figs. 1–4: cellular/liver activity, durability, repeat dosing and rat results — Original source figures.

References and source locations

Finn JD, Smith AR, Patel MC et al. A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing. Cell Reports 22, 2227–2235 (2018). DOI: 10.1016/j.celrep.2018.02.014.