Illustration of a lipid nanoparticle with PEG chains on its surface, one carrying a targeting ligand

NOF’s LNP Platform

Platform Highlights

  • Targeting

    Organs: liver, spleen and lung

    Immune cells: macrophages, NK cells, dendritic cells and T cells

    Icons of the liver, spleen and lung beside drawings of a macrophage, an NK cell, a dendritic cell and a T cell

  • Tolerability

    • Safety profile in non-human primates (NHPs)
    • Reduced adverse reaction
    • Rat biliary/urinary excretion

  • Application

    • Gene editing
    • Vaccine
    • Immune disease treatment

  • CMC Development

    • Scalable manufacturing
    • Conjugation chemistry
    • Frozen / lyophilized LNP

NOF Offers

Seamless Support from Discovery to Clinical Development

  • Proprietary Ionizable Lipid Library
  • Formulation Optimization with Materials Informatics Platform
  • GMP Grade Lipid Supply
  • Active Targeting

  1. Lipid Library

  2. LNP Discovery

  3. NHP Study

  4. Clinical Trial

In Vivo Data

Explore the Data

Study summaries from non-human primate and rodent models. Select any figure to enlarge it.

Overview

mRNA Delivery in Non-Human Primates

Lung Delivery in Cynomolgus Monkeys

Cynomolgus monkey

Study design

  • Animals: cynomolgus monkeys, 7–8 years, female
  • Formulation: Fluc mRNA in lung-tropic LNP
  • Dose: 0.04–0.4 mg mRNA/kg, I.V.
  • Readouts: tissues collected at 6 h and imaged by IVIS after luciferin; homogenization and cell sorting for Western blot (WB)
Study timeline: LNP injection at 0 hours, tissue collection at 6 hours, luciferin and IVIS imaging, then homogenization or cell sorting for Western blot

Luciferase expression by tissue (IVIS)

Bar chart of IVIS photon flux by tissue at 0.4 and 0.04 mg/kg. The lung shows the highest signal, roughly 7 × 10⁶ photons/s/cm²/sr at the high dose and 1.7 × 10⁶ at the low dose, followed by the spleen; other tissues are near zero.

Photon flux (photons/s/cm²/sr) at 0.4 mg/kg, 0.04 mg/kg and vehicle control.

Densitometric analysis (lung epithelial cells)

Bar chart of Western blot signal normalized to input in lung epithelial cells: about 75 for the high dose versus about 59 for vehicle.

Western blot signal normalized to input, high dose vs. vehicle.

Key finding

Dose-dependent mRNA delivery and translation in the lung.

mRNA Delivery in Non-Human Primates

Liver Delivery in Cynomolgus Monkeys

Cynomolgus monkey

Study design

  • Animals: cynomolgus monkeys, 2–4 years, male
  • Formulation: hEPO mRNA + ncRNA in liver-tropic LNP
  • Dose: 2 mg RNA/kg, I.V. infusion over 60 min
  • Sampling: blood before dosing and at 6, 12, 24, 48, 72 and 168 h for serum hEPO by ELISA
Study timeline: pre-dose blood sample, I.V. infusion at 0 hours, and blood collection at 6, 12, 24, 48, 72 and 168 hours for serum analysis

Serum hEPO PK profiles (ELISA)

Line chart of serum hEPO activity over 168 hours. SS-OP peaks near 8,900 mIU/mL at about 12 hours, while Competitor lipid B peaks near 2,000 mIU/mL and Competitor lipid C near 2,900 mIU/mL.

Serum hEPO activity (mIU/mL) after SS-OP, Competitor lipid B and Competitor lipid C LNPs.

Key finding

SS-OP outperforms Competitor lipids B and C in mRNA translation in NHPs.

Non-Human Primates

Safety Profile

Cynomolgus monkey

Study design

  • Animals: cynomolgus monkeys, 2–4 years, male and female
  • Dose: 2 mg RNA/kg, I.V. infusion over 60 min
  • Sampling: blood before dosing and at 6, 12, 24, 48, 72 and 168 h for serum analysis
  • Comparison: SS-OP vs. Competitor lipid B and Competitor lipid C
Study timeline: pre-dose blood sample, infusion at 0 hours, and blood collection at 6, 12, 24, 48, 72 and 168 hours

ALT

Bar chart of serum ALT from pre-dose to 168 hours. SS-OP and Competitor lipid B stay at or below about 80 U/L, while Competitor lipid C rises to about 195 U/L.

Serum ALT (U/L), pre-dose to 168 h.

AST

Bar chart of serum AST from pre-dose to 168 hours. SS-OP peaks at about 205 U/L, Competitor lipid B at about 200 U/L and Competitor lipid C at about 245 U/L.

Serum AST (U/L), pre-dose to 168 h.

Anti-PEG IgG production

Line chart of serum anti-PEG IgG activity from day 0 to day 7 in male and female animals. Competitor lipid B (female) rises to about 4,500 U/mL and Competitor lipid C (male) to about 1,600 U/mL, while SS-OP stays near baseline.

Serum anti-PEG IgG activity (U/mL), days 0–7, male and female.

Cytokine induction profiles across LNP formulations at 6 hours post-injection

Heat map of row Z-scores for 26 cytokines in non-treated, SS-OP, Competitor lipid B and Competitor lipid C groups. Competitor lipid C is high for most pro-inflammatory cytokines and chemokines, Competitor lipid B for hematopoietic factors and several lymphocyte activation markers, and SS-OP stays low, close to non-treated.

Row Z-scores for pro-inflammatory cytokines, chemokines, hematopoietic factors, lymphocyte activation markers, cytotoxic effectors and other mediators. Values below the detection limit were set to half of the lower limit of quantification (LLOQ).

Key finding

SS-OP provides an optimal safety profile: it mitigates both the hepatotoxicity (ALT/AST elevation) and immunotoxicity (pro-inflammatory cytokine elevation), and avoids the high anti-PEG IgG induction seen in Competitor lipids B and C.

mRNA Delivery in Mice

Spleen Delivery

BALB/c mouse

Study design

  • Animals: BALB/c mice, 7–10 weeks, I.V.
  • Formulation: Fluc or GFP mRNA in spleen-tropic LNP
  • Dose: 0.5 mg mRNA/kg
  • Readouts: tissue collection and IVIS imaging at 6 h; spleen collection at 24 h, dissociation and RBC lysis for flow cytometry (FCM)
Study timeline: injection at 0 hours, tissue collection for IVIS at 6 hours, and spleen collection at 24 hours followed by dissociation, RBC lysis and flow cytometry

NOF’s Splenic Formulation

NOF’s splenic formulation using SS-OP (Splenic-SSOP) exhibits strong spleen tropism.

Liver and spleen IVIS images

IVIS images of liver and spleen. Std-LNP (Competitor lipid A) gives a strong liver signal and a weak spleen signal; Splenic-SSOP gives a weak liver signal and a strong spleen signal.

Std-LNP (Competitor lipid A) vs. Splenic-SSOP.

GFP-positive splenic cells (FCM)

Bar charts of GFP-positive NK cells, dendritic cells and macrophages for NT, Std and Splenic-SSOP. Splenic-SSOP reaches about 14% of dendritic cells and 12% of macrophages, with about 1% of NK cells.

Splenic-SSOP formulation targets DCs and macrophages in the spleen.

Collaboration with Cytodigm

Cytodigm’s Cytofinity™ combined with SS-OP (Cyto-SSOP) further enhances the spleen tropism.

Liver and spleen IVIS images

IVIS images of liver and spleen. Std-LNP (Competitor lipid A) gives a strong liver signal; Cyto-SSOP gives almost no liver signal and a strong spleen signal.

Std-LNP (Competitor lipid A) vs. Cyto-SSOP.

GFP-positive splenic cells (FCM)

Bar charts of GFP-positive NK cells, dendritic cells and macrophages for NT, Std and Cyto-SSOP. Cyto-SSOP reaches about 12% GFP-positive NK cells, well above NT and Std.

Cyto-SSOP targets NK cells.

Key finding

SS-OP delivers mRNA to NK cells / DCs / macrophages in the spleen depending on formulation designs.

mRNA Vaccine

Low-Inflammatory mRNA Influenza Vaccine

C57BL/6J mouse

Study design

  • Animals: C57BL/6J mice, 6–7 weeks, male, I.M.
  • Antigen: hemagglutinin (HA) mRNA
  • Dose: 0.05 or 0.25 mg mRNA/kg
  • Schedule: prime on day 0 and boost on day 21; plasma cytokines and rectal temperature measured after each dose; plasma antibodies quantified on day 35
Study timeline: prime on day 0, boost on day 21 and plasma antibody quantification on day 35, with plasma cytokine and rectal temperature measurements after each dose

HA-specific IgG1 (boost)

Scatter plot of HA-specific IgG1 optical density after the boost at plasma dilutions of 1:2,000, 1:10,000 and 1:50,000. SS-OP and SM-102 give similar values, about 1.0 to 1.1 OD at 1:2,000, both far above PBS.

0.05 mg/kg. Plasma dilutions 1:2,000, 1:10,000 and 1:50,000.

IFN-α

Scatter plot of plasma IFN-alpha after prime and boost. SS-OP stays below about 300 pg/mL, while SM-102 averages about 900 to 1,000 pg/mL.

0.05 mg/kg. Plasma IFN-α (pg/mL) after prime and boost.

Rectal temperature (boost)

Scatter plot of rectal temperature after the boost. PBS and SS-OP average about 36.2 °C, while SM-102 averages about 36.9 °C.

0.25 mg/kg. Rectal temperature (°C) after the boost.

Key findings

  • Antigen-specific IgG production: SS-OP = SM-102
  • Inflammatory cytokine production: SS-OP < SM-102

ns: not statistically significant; ***: p < 0.001; ****: p < 0.0001.

The “SS-OP” and “SM-102” notations in the figures in this section are modified from “LNP ssPalmO” and “LNP SM-102” in the reference: Kawai et al., Low-inflammatory lipid nanoparticle-based mRNA vaccine elicits protective immunity against H5N1 influenza virus with reduced adverse reactions, Molecular Therapy (2024), https://doi.org/10.1016/j.ymthe.2024.12.032. Molecular Therapy Vol. 33 No 2 February 2025 © 2024 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Ligand-Modified LNPs

Active Targeting

Mouse

Post-modification by click reaction

Schematic of post-modification: an LNP carrying DBCO groups is incubated with an azide-modified antibody at 4 °C for about 2 hours, giving an antibody-modified targeted LNP.

ntLNP: non-targeted LNP. tLNP: lymphatic EC-targeted, anti-PDPN antibody-modified LNP.

Antibody-mediated cell-type specific uptake

Flow cytometry histograms of DiD-LNP fluorescence. In lymphatic endothelial cells, tLNP shows higher fluorescence than ntLNP, which stays close to PBS. In blood endothelial cells, ntLNP shows higher fluorescence than tLNP.

DiD-LNP fluorescence in lymphatic ECs (CD31⁺/PDPN⁺) and blood ECs (CD31⁺/PDPN⁻).

Selective localization to lymphatic ECs

Fluorescence micrographs of lymphatic vessels for ntLNP and tLNP, with merge, LNP (DiD), PDPN and CD31 channels. tLNP shows a strong green DiD signal along the PDPN-positive vessel; ntLNP shows little LNP signal.

Lymphatic ECs; CD31⁺/PDPN⁺ region. Columns show ntLNP and tLNP; rows show the merged image, LNP (DiD), PDPN and CD31.

Key finding

tLNP containing SS-OP clearly targets the lymphatic ECs, indicating that SS-OP is applicable for targeted (ligand-modified) LNPs.

NOF’s Proprietary Lipid Library

Rodent Studies Using Our Novel Lipid Library

BALB/c mouse

Gene Expression in the Liver

BALB/c mice, 6–7 weeks, female, I.V. Fluc mRNA in liver-tropic LNP at 0.05 mg mRNA/kg; tissues collected for IVIS at 4 h.

Study timeline: injection at 0 hours and tissue collection for IVIS at 4 hours
Bar chart of total liver flux at 4 hours. Vehicle is near zero, SS-OP is about 1.3 × 10⁹ p/s, and eight library lipids range from about 4.5 × 10⁹ to 1.0 × 10¹⁰ p/s.

Total flux at 4 h post injection (p/s).

Hepatotoxicity

BALB/c mice, 6–7 weeks, female, I.V. Empty liver-tropic LNP at 230 mg ionizable lipid/kg; plasma collected at 24 h for hepatotoxicity assays.

Study timeline: injection at 0 hours and plasma collection at 24 hours for hepatotoxicity assays
Bar chart of plasma ALT and AST at 24 hours with upper normal limits of about 65 U/L for ALT and 95 U/L for AST. Vehicle, SS-OP and the library lipids stay below the AST limit, and one library lipid reaches the ALT limit.

Enzyme activity at 24 h post injection (U/L).

Key finding

Library compounds demonstrate high gene expression activity with toxicity levels comparable to SS-OP.

Information

Articles and Patents

Liver delivery

(1) Hepatic pDNA delivery M. Ukawa et al., Adv. Healthc. Mater., 3, 1222–1229 (2014). doi:10.1002/adhm.201300629

(2) Hepatic mRNA delivery by SS-OP LNP H. Tanaka et al., Adv. Funct. Mater., 30, 1910575 (2020). doi:10.1002/adfm.201910575

Spleen delivery

(3) Splenic mRNA delivery by PS loaded LNPs M. Gomi et al., Adv. Healthc. Mater., 12, e2202528 (2023). doi:10.1002/adhm.202202528

(4) Self-antigen mRNA delivery for treatment of EAE model M. Gomi et al., Pharmaceuticals, 16, 1270–1281 (2023). doi:10.3390/ph16091270

Brain delivery

(5) Efficient mRNA transfection in brain capillary endothelial cells Y. Sakurai et al., Pharmaceutics, 14, 1560–1571 (2022). doi:10.3390/pharmaceutics14081560

Vaccine (cancer and infection)

(6) mRNA vaccine for infectious diseases A. Kawai et al., Mol. Ther., 33, 529–547 (2025). doi:10.1016/j.ymthe.2024.12.032

(7) RNA cancer vaccine J. Anindita et al., J. Control. Release, 389, 114414 (2026). doi:10.1016/j.jconrel.2025.114414

Active targeting (ligand-modified LNP)

(8) Lung delivery by peptide ligand LNP (I.V.) S. Santiwarangkool et al., J. Pharm. Sci., 106, 2420–2427 (2017). doi:10.1016/j.xphs.2017.04.075

(9) Targeted delivery of LNP to lymphatic endothelial cells Y. Sakurai et al., J. Control. Release, 349, 379–387 (2022). doi:10.1016/j.jconrel.2022.06.052

In vitro transfection

(10) In vitro pDNA delivery H. Akita et al., Adv. Healthc. Mater., 2, 1120–1125 (2013). doi:10.1002/adhm.201200431

(11) Efficient mRNA transfection in T cell line H. Tanaka et al., Pharmaceutics, 13, 2097–2112 (2021). doi:10.3390/pharmaceutics13122097

Patents

(1) Cationic lipid having improved intracellular kinetics Patent numbers: US9708628, EP2781507, JP6093710, CN201280056417.9

(2) Cationic lipid Patent numbers: US10385030, EP3252043, JP6640750, CN107406396

(3) Novel cationic lipid exhibiting improved intracellular dynamics Application number: WO2019188867A1

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