Custom mRNA-LNPs/siRNA-LNP/ASO-LNP Synthesis
The RNA Medicine Core offers siRNA-LNP, ASO-LNP, mRNA-LNP, and circRNA-LNP synthesis services. We support RNA-LNPs preparation for dry run tests (i.e., 2-50 µg of mRNA/custom RNAs/siRNA/ASO), in vitro scale (50 µg ~ 500 µg of mRNA/custom RNAs/siRNA/ASO), and in vivo scale (> 500 µg ~ 15 mg of mRNA/siRNA/ASO). Additionally, our patented lipids enable the creation of near-infrared (NIR) fluorescent-labeled LNPs, which facilitate the in vivo visualization of LNP distribution, making it easier to track the biodistribution and targeting efficiency of RNA-LNPs.
What We Offer
Catalog | Gene | Dry Run | In vitro Scale | In vivo Scale | Post purification & QC tests | Storage & Shelf Life | Timeline (Business days) |
|---|---|---|---|---|---|---|---|
siRNA LNP Kit | Custom gene | Client Spec (1 - 3 nmol) | / | / | No | freshly use | 1 |
mRNA LNP Kit | Custom gene | Client Spec (2 - 10 ug) | / | / | No | freshly use | 1 |
lncRNA-LNP | Custom gene | Client Spec (< 10 ug) | >= 100 ug | >500 ug | Yes | 4 °C, 3 months, sterile, open inside BSC | 3 |
circRNA-LNP | Custom gene | Client Spec (<10 ug) | >= 100 ug | >500 ug | Yes | -80 °C, 3 months, sterile, open inside BSC | 3 |
ASO-LNP | Custom gene | Client Spec (>=3 nmol) | >=10 nmol | >150 nmol | Yes | 4 °C, 3 months, sterile, open inside BSC | 3 |
siRNA-LNP | Custom gene | Client Spec (>=3 nmol) | >=10 nmol | >150 nmol | Yes | 4 °C, 3 months, sterile, open inside BSC | 3 |
mRNA-LNP | Custom gene | Client Spec (<10 ug) | >= 100 ug | >500 ug | Yes | -80 °C, 3 months, avoid multiple freeze thaw cycles | 3 |
mRNA-LNP | Reporter gene mRNA | / | >= 100 ug | >500 ug | Yes | -80 °C, 3 months, avoid multiple freeze thaw cycles | 1-3 |
Quality-Driven Potency Testing
Formulation & Pharmacology
Chemistry & Formulation of RNA-LNPs
LNPs typically contain 4 components: ionizable lipids (for siRNA/mRNA encapsulation), phospholipids (structural), cholesterol (membrane stability), and PEG-lipids (stealth properties). Formulated through controlled mixing processes creating ~100nm particles.
Pharmacology of mRNA-LNP
Biodistribution: Primarily accumulate in liver, spleen, and injection site. 30–90% of intravenously administered LNPs become entrapped in the liver’s sinusoid lumen and Disse’s space. Limited brain penetration due to blood-brain barrier. Varies in different administration routes.
Half-life: Plasma half-life ranges 1-6 hours depending on administration route and formulation. mRNA expression peaks 6-24 hours post-injection.
Clearance mechanisms: Hepatic uptake by Kupffer cells, renal filtration of small components, and enzymatic degradation of mRNA by RNases.
Toxicity: Generally well-tolerated (0.005–0.250 mg/kg) mRNA. Potential issues include transient inflammation, complement activation, and rare allergic reactions. Dose-dependent hepatotoxicity observed at high doses.
mRNA Cargo capacity: Typically 1-5% mRNA by weight. Encapsulation efficiency usually 80-95%. Optimal N/P ratio (nitrogen to phosphate) around 3-6 for stable complexation.
Pharmacology of siRNA-LNP
Biodistribution: With a single intravenous dose of siRNA-LNP, approximately 90% of the administered radioactivity was detected in the liver 4 hours after administration (based on 14C-labeled ionizable lipid studies in rats)
Half-life: Plasma half-life ranges 3-6 hours in mice.
Toxicity: Generally well-tolerated 1-5 mg siRNA/kg body weight in mice.
siRNA Cargo capacity: Typically 1:10-20 siRNA:lipid weight ratio. Encapsulation efficiency usually 80-95%. Optimal N/P ratio (nitrogen to phosphate) around 3-6 for stable complexation.
References and more information about mRNA-LNP and siRNA-LNP Patent Summary
LNP Category | Formulation | Molar Ratio |
|---|---|---|
Custom RNA-LNPs | Client Spec | Client Spec |
siRNA-LNP/ASO-LNP | Dlin-MC3-DMA/DSPC/Cholesterol/PEG2000-DMG | 50/10/38.5/1.5 |
mRNA-LNP/circRNA-LNP | SM102/DSPC/Cholesterol/PEG2000-DMG | 50/10/38.5/1.5 |
RNA-LNPs Quality Control
QC | QC Method | Specification | Regular Test | Add-on |
|---|---|---|---|---|
Lipid composition | UPLC-ELSD | No | Yes | |
Endotoxin | Limulus Amebocyte Lysate assay | No | Yes | |
Encapsulate Efficiency | RiboGreen Assay | >90% | Yes | No |
Particle size | Dynamic Light Scattering | <120nm | Yes | No |
Particle Uniformity | Dynamic Light Scattering | <0.2 | Yes | No |
Concentration | RiboGreen Assay | Client Spec | Yes | No |