Six lipid nanoparticle formulations for mRNA delivery compared in primates using 30 microliters of serum
Six lipid nanoparticle formulations for mRNA delivery compared in primates using 30 microliters of serum
On 11 August, Nature Biotechnology published a description of snapCodes. The method can compare six lipid nanoparticle formulations, which serve as lipid shells for delivering mRNA instructions for protein production, in a single nonhuman primate using a 30 microliter, or 0,03 milliliter, serum sample.
The composition of the lipid shell affects every step of delivery: whether the mRNA travels from the bloodstream into a cell, whether it is released inside the cell, and whether the cell can use the instructions to produce a protein. Researchers first screen different formulations in cells and mice, but candidates may rank differently in mice and primates. Comparing delivery vehicles in primates is therefore a separate stage of development.
In a 2025 study from the same line of research, the researchers had already administered a mixture of 45 lipid nanoparticle formulations to a single primate. To read the barcodes, they isolated cells from the liver, spleen, bone marrow, and blood. The authors described the cost of conducting such a comparison:
“A hypothetical study testing 45 LNP in three animals per formulation could take several years, cost a great deal, and result in the deaths of 135 animals, even before including control groups.”
SnapCodes move the readout into serum. Each of the six delivery vehicle formulations contained mRNA encoding a SNAP-tagged protein and its own DNA snapCode. The researchers attached benzylguanine, a chemical label that forms a stable bond with the SNAP tag, to the code. If the vehicle delivered the mRNA, the cell produced the protein, and the attached code could then be detected in serum. Sequencing, which reads the order of DNA letters, showed which formulation delivered the mRNA successfully enough for the cell to produce the encoded protein.
The authors first validated this sequence of events in control experiments, then administered six formulations intravenously to mice and nonhuman primates. The method can rank delivery vehicle formulations by functional mRNA delivery in a single primate using a readout from 30 microliters of serum. The authors propose using this test to select formulations for subsequent studies.