DC Chemicals

DC49882 · Updated 28 October 2026

cKK-E12

Literature evidence · DC49882

Formulation & Performance

The 2014 PNAS paper provides mouse, rat and nonhuman-primate siRNA evidence. Rodent ED50 values, cell-selectivity experiments and the monkey fixed-dose TTR result are shown separately.

DC49882 is cKK-E12. The catalog molecular weight 993.62 is retained. This module reports the original siRNA study; results from later mRNA formulations are not merged into its formulation record.

Formulation components and molecular-weight conversion

ComponentDC Chemicals productMolecular weightMolar ratioMass at 1 µmol total lipid (mg)
cKK-E12DC49882993.62Not assignedNot calculable from disclosed data
DSPCDC57005790.15Not assignedNot calculable from disclosed data
CholesterolDCD-041386.65Not assignedNot calculable from disclosed data
PEG-lipid (identity unassigned)Not uniquely mappedNot establishedNot assignedNot calculable from disclosed data

Main text identifies cKK-E12, DSPC, cholesterol and a PEG-lipid. The complete 2014 SI was not retrieved, so molar ratios, PEG identity/MW, N/P and lipid:RNA mass ratio are not assigned. A familiar 50:10:38.5:1.5 recipe is not assumed to be the verified original formulation.

Component mass calculator

Not all inputs are assigned to a single verified study formulation; unassigned fields are blank. Enter your own values to calculate a research scenario. Molecular weights and ratios are editable. Results are calculated, not measured study data. No N/P or RNA dose is inferred.

ComponentMWMolar ratioMass (mg)Mass %
cKK-E12——
DSPC——
Cholesterol——
PEG-lipid (identity unassigned)——

Formulation and physical characterization

Study / parameterReported evidenceSource / interpretation
Reported component classescKK-E12 / DSPC / cholesterol / PEG-lipid with siRNAMain Results; complete proportions remain unverified
DLS diameterApproximately 70 nmMain text and Fig. 2; approximate study value
Cryo-TEMParticles approximately 35–85 nmMain Fig. 2; imaging and hydrodynamic size are different measurements
Unassigned parametersExact PEG identity, proportions, N/P, encapsulation percentage and PDIComplete original SI required before these values are prefilled

Rodent siRNA potency

Study / parameterReported evidenceSource / interpretation
Mouse FVIIED50 approximately 0.002 mg/kg entrapped siRNAMain Fig. 2; a factor VII silencing endpoint
Rat FVIIED50 below 0.01 mg/kg siRNAMain Results; species-specific potency estimate
Dose interpretationValues are siRNA dose-based, not lipid dose-basedNot an mRNA expression dose or reporter-editing percentage
Benchmark interpretationThe paper compares dose-response profiles of multiple delivery systemsDo not rank every application by one FVII assay

Cell selectivity and uptake mechanism

Study / parameterReported evidenceSource / interpretation
Pten silencing0.1 mg/kg siRNA produced >80% silencing in mouse hepatocytesMain Fig. 4; cell-resolved Pten experiment
Other liver populationsNo significant Pten silencing in endothelial cells or leukocytes at that doseSame Pten experiment; not an absolute ban on extrahepatic delivery
Separate target assaysTie2 and CD45 studies used 1 mg/kg and gave weaker cell-population responsesMain Fig. 4; different genes/doses cannot be treated as a single selectivity ratio
Apolipoprotein EApoE enhanced uptake/potency; activity fell in ApoE-deficient mice but remained in LDLR-deficient miceMain Fig. 5; supports an ApoE-associated mechanism without requiring LDLR alone

Nonhuman-primate TTR silencing

Study / parameterReported evidenceSource / interpretation
Species and cohortCynomolgus monkeys; n = 3Main Fig. 6
TreatmentSingle intravenous infusion of 0.3 mg/kg siTTR-containing LPNs15-minute infusion in the reported study
MeasurementLiver biopsy at 48 h; TTR mRNA measured relative to GAPDHMain Fig. 6; liver transcript endpoint
OutcomeGreater than 95% TTR mRNA silencing0.3 mg/kg is a tested effective dose, not a reported primate ED50
ScopeNo clinical response or long-term primate safety conclusion is established by this resultDo not equate liver mRNA silencing with serum protein reduction

Tolerability and remaining evidence gaps

Study / parameterReported evidenceSource / interpretation
Rat tolerabilityPaper reports tolerability at 1 mg/kg siRNASupporting toxicology Table S2 was not independently retrieved
Safety margin descriptionPaper describes a dose above 100 times the rat FVII ED50Study-specific comparison; not a validated human therapeutic index
Published correctionThe 2014 correction adds funding acknowledgmentsDOI 10.1073/pnas.1404711111; no efficacy-data correction described
Remaining gapsComplete original SI and exact formulation mappingNo invented NOAEL, immune-response panel or recipe

Original study figures

Original Figs. 2, 4–6: particle properties, cell selectivity, ApoE and monkey TTR response — Original source figures.

References and source locations

  1. Dong Y, Love KT, Dorkin JR et al. Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates. PNAS 111, 3955–3960 (2014). DOI: 10.1073/pnas.1322937111.
  2. Correction: additional funding acknowledgments. PNAS 111, 5753 (2014). DOI: 10.1073/pnas.1404711111.