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Detection of Intracellular Gene Expression in Live Cells of Murine, Human and Porcine Origin Using Fluorescence-labeled Nanoparticles
Published on: November 13, 2015
Non-invasive nanoparticle barcoding in nonhuman primates
Bora Jang1, Ryan Zenhausern1, Liming Lian1
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA, USA.
Nature Biotechnology
|August 11, 2026
Summary
We developed a non-invasive method to track lipid nanoparticle (LNP) mRNA delivery in nonhuman primates using just serum. This approach reduces animal use and speeds up the identification of effective nanoparticle drug delivery systems.
Area of Science:
- Biotechnology
- Pharmacology
- Molecular Biology
Background:
- Lipid nanoparticle (LNP)-mRNA drug candidates' clinical relevance is often assessed in nonhuman primates.
- Evaluating chemically distinct LNPs in nonhuman primates is challenging due to invasive nanoparticle barcoding assays requiring euthanasia and complex tissue processing.
Purpose of the Study:
- To develop a non-invasive method for quantifying functional mRNA delivery by multiple lipid nanoparticles (LNPs) in a single nonhuman primate.
- To reduce animal use and streamline the evaluation of LNP formulations for drug delivery.
Main Methods:
- Developed "snapCodes", benzylguanine-modified DNA barcodes that bind to mRNA-encoded nanoluciferase-SNAP-tag fusion proteins in vivo.
- Isolated DNA-fusion protein complexes from serum after intravenous administration of six snapCoded LNPs to mice and nonhuman primates.
- Quantified functional mRNA delivery non-invasively using a small volume of serum (30 µl) and DNA sequencing.
Main Results:
- Successfully validated snapCode and fusion protein activity.
- Demonstrated the ability to compare LNP delivery across species (mice and nonhuman primates) non-invasively.
- Quantified mRNA delivery from multiple LNPs in a single nonhuman primate using a low-volume blood draw.
Conclusions:
- Non-invasive nanoparticle barcoding using snapCodes enables efficient evaluation of LNP-mediated mRNA delivery in nonhuman primates.
- This method reduces animal use and facilitates the identification of promising nanoparticle formulations for therapeutic applications.
