Lipid Nanoparticle: the leading non-viral vector for in-vivo gene delivery
LNP success in COVID-19 mRNA vaccines proved the technology platform at population scale. The same physics drives therapeutic gene editing delivery — with tighter formulation tolerances.
LNP properties at a glance
| Property | Typical Range | Optimal for Hepatic Editing | What Gendelivr Screens |
|---|---|---|---|
| Particle size (Z-avg) | 60–250 nm | 80–130 nm | 80–150 nm pre-filter |
| Polydispersity index (PDI) | 0.05–0.30 | <0.15 | Predicted PDI, filtered <0.20 |
| Ionizable lipid pKa | 5.5–7.5 | 6.2–6.8 | Full pKa prediction per candidate |
| Encapsulation efficiency | 60–95% | >80% | Predicted EE, filtered >70% |
| Zeta potential (pH 7.4) | −30 to +30 mV | −5 to +5 mV | pKa-derived surface charge estimate |
Microfluidic ethanol injection
GMP-compatible LNP manufacturing via microfluidic mixing is now well-established. The process is straightforward — the bottleneck has always been formulation selection.
Lipid stock preparation
Ionizable lipid, helper lipid, cholesterol, and PEG-lipid dissolved in ethanol at the target molar ratio. mRNA dissolved in citrate buffer (pH 4.0).
Microfluidic mixing
Lipid stream (ethanol) and mRNA stream (aqueous) combine in a microfluidic mixing chip at controlled flow rate ratio (1:3 ethanol:aqueous). Self-assembly occurs at the interface.
Dialysis and concentration
Ethanol removal by dialysis into PBS (pH 7.4). Tangential flow filtration for concentration and buffer exchange. DLS and Ribogreen assay for size, PDI, and encapsulation efficiency QC.
Release QC and storage
Appearance, osmolality, endotoxin, and in vitro potency release testing. Storage at −80°C in 10% sucrose cryoprotectant until use.
Optimize your LNP formulation before bench synthesis
Gendelivr screens 10,000 formulations in silico and delivers your bench-ready top-10 candidate list — with synthesis protocols ready for your CDMO.