p53

p53-LNP Designer / Formulation Workbench

In silico · empirical + pKa models · build 0x9C2F

Validation →

p53-LNP Designer — in silico lipid nanoparticle formulation platform

Recommended formulation

DLin-MC3-DMA · R175H p53-mRNA

Alnylam / Onpattro · Approved · tertiary amine

02

Ionizable

50.0%

pKa 6.44

Helper · DSPC

10.0%

saturated C18 · lamellar stabiliser

Cholesterol

38.5%

membrane rigidity

PEG-lipid

1.5%

DMG-PEG2000

Encapsulation97.0%
Endosomal escape96.0%
Particle size92.1 nm
PDI0.078
delivery score 93.2model confidence 96.0%N/P 6.0 · 3.0:1 @ 8.0 mL/min

Targeting ligand

Phase II

Folate · FR-α

FR-α overexpressed in 80% of epithelial ovarian tumours · affinity 0.8 nM

Top-3 alternate lipids

03
  1. 1

    TT3 (FTT5)

    pKa 6.35 · escape 91%

    97%

  2. 2

    L319

    pKa 6.25 · escape 93%

    97%

  3. 3

    306Oi10

    pKa 6.55 · escape 87%

    97%

3D particle cross-section

molecular viewer →
mRNA core · 97% encapsulatedD₅₀ 92 nm · PDI 0.078 · drag to orbit

Microfluidic alignment

04

Droplets snap into monodisperse alignment · flow 3.0:1, 8.0 mL/min · D₅₀ 92.1 nm

Ionizable lipid library

05
pKa5.507.50
LipidpKalogPTailEncap.SizePDIEscapeScoreStatus
DLin-MC3-DMAAlnylam / Onpattro6.444.8C18:2 x297%92 nm0.07896%93selected
TT3 (FTT5)Dong lab6.354.3C15 branched97%89 nm0.08091%92preclinical
L319Alnylam6.254.5C18:2 ester97%92 nm0.08393%92preclinical
306Oi10Anderson lab6.554.4C10 branched97%85 nm0.08087%91preclinical
Lipid 5Moderna6.564.9C9/C8 ester97%91 nm0.08087%90preclinical
C12-200Anderson lab6.203.9C12 x597%87 nm0.08584%90preclinical
A18-Iso5-2DC18Xu lab6.605.0C18 x297%92 nm0.08184%89preclinical
cKK-E12Anderson lab6.143.7C12 x497%87 nm0.08979%88preclinical
DLin-KC2-DMATekmira6.104.6C18:2 x297%92 nm0.09181%88phase i
SM-102Moderna / Spikevax6.684.2C10/C7 ester97%91 nm0.08477%87approved
ALC-0315Acuitas / Comirnaty6.095.1C14 branched97%89 nm0.09274%86approved
BAMEA-O16BDong lab6.754.7C16 disulfide97%90 nm0.08871%84preclinical
9A1P9Siegwart lab6.904.1C9 ester97%84 nm0.09856%80preclinical
OF-Deg-LinWhitehead lab5.804.0C18:2 oxidized91%92 nm0.11354%76preclinical
SS-33/4PE-15Harashima lab7.155.3C15 disulfide89%89 nm0.11639%70preclinical
15 of 15 lipids · sorted by delivery score ↓ · click a row to pinPredictions are in silico — validate in vitro before use.