Nature biotechnologyAug 11, 2026

Using harmless nanoparticles to track cells in monkeys

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 13, 2026

Abstract

Non-invasive nanoparticle barcoding successfully quantifies mRNA delivery in a single nonhuman primate using 30 µl of serum.

This method utilizes snapCodes, which are modified DNA barcodes that bind to a specific fusion protein to track mRNA delivery.
The approach allows for the isolation and sequencing of DNA-fusion protein complexes from serum without the need for euthanasia.
The study compares the delivery of six chemically distinct lipid nanoparticles (LNPs) in both mice and nonhuman primates.
Using a low-volume blood draw for mRNA delivery measurement could reduce the number of animals needed for testing.
Preliminary findings suggest that this non-invasive technique may aid in identifying effective nanoparticle formulations.

Simplified

The clinical relevance of a lipid nanoparticle (LNP)-mRNA drug candidate is often dictated by its behavior in nonhuman primates. Yet, evaluating how chemically distinct LNPs behave in nonhuman primates remains difficult, in part because nanoparticle barcoding assays require euthanasia and difficult downstream tissue processing. Here we report non-invasive nanoparticle barcoding, which quantifies functional mRNA delivery mediated by several LNPs in a single nonhuman primate using 30 µl of serum. This method is enabled by snapCodes, benzylguanine-modified DNA barcodes that covalently bind an mRNA-encoded nanoluciferase-SNAP-tag fusion protein in vivo. The resulting DNA-fusion protein complexes are exported from cells, isolated from serum and sequenced. After validating snapCode and fusion protein activity, we intravenously administer six snapCoded LNPs to mice and nonhuman primates, thereby comparing LNP delivery across species. Measuring mRNA delivery from multiple LNPs using a low-volume blood draw reduces animal use and may help identify promising nanoparticle formulations.