Lipid Nanoparticle-Mediated mRNA Delivery

Lipid nanoparticle delivery of mRNA-1273 and spike protein expression in host cells

I’ll pull up key papers on how mRNA-1273’s lipid nanoparticles deliver mRNA into cells and what’s known about the kinetics/location of spike protein expression after vaccination.

Ran analysis

• 4 searches
  • MRNA-1273 lipid nanoparticle biodistribution spike protein expression
  • MRNA-1273 vaccine spike expression draining lymph node antigen presenting cells
  • Intramuscular mRNA lipid nanoparticle biodistribution luciferase preclinical
  • COVID-19 mRNA vaccine spike protein expression muscle cells dendritic cells

From a quick scan, the clearest picture is that mRNA-1273’s LNPs mainly stay near the injection site and nearby lymphoid tissues, and spike expression is transient (days, not weeks), with the most direct spike-kinetics data coming from animal biodistribution work.

Mechanistically, the LNP’s ionizable lipid is central to delivery: it packages the mRNA, supports cell uptake, and helps endosomal escape so the mRNA reaches the cytosol for translation. Ren et al. 2025

For where the vaccine goes after intramuscular injection, a rat biodistribution preprint comparing mRNA-1273 to other mRNA-LNP products reports the highest exposures at the injection site, draining lymph nodes, and spleen. Goody et al. 2026 Imaging/trafficking work in mice and non-human primates similarly sees LNPs spreading through injected muscle and rapidly reaching draining lymph nodes; in that NHP work, antigen-presenting cells are the main early cell type implicated in uptake/translation. Buckley et al. 2024 In rodents, one study that explicitly quantified trafficking/expression after i.m. dosing found vaccine mRNA mostly present at ~24 h and then rapidly degraded, while expressed protein in draining lymph nodes localized strongly to subcapsular/medullary sinus macrophages. Hassett et al. 2023 A separate mouse study argues that delivery/transfection in secondary lymphoid organs, more than expression in muscle per se, is what drives adaptive responses (shown using reporter and antigen constructs). Takanashi et al. 2023

For spike protein expression kinetics specifically, the most direct claim I found tied to mRNA-1273 in vivo is that spike protein levels were “transiently observed” and cleared in under about 5 days in an infection-free rat model, without accumulation after repeated dosing. Goody et al. 2026 Human data are thinner and method-dependent: a 2026 post-mortem study reports vaccine-related mRNA/spike detectable at the vaccination site, with “muscle-associated fibroblasts” as a major source of spike expression, and it reports no detectable vaccine-related mRNA/spike in extramuscular organs in the humans they examined (while mice did show detection in multiple organs up to 7 days). Heinrich et al. 2026 In parallel, a Moderna booster pharmacokinetics preprint reports that both vaccine mRNA and ionizable lipid peak in blood 1–2 days post-vaccination and that mRNA can remain detectable in blood for 14–28 days; that establishes some systemic circulation of vaccine components in humans, but it does not, by itself, tell you where (or whether) spike is being translated. Kent et al. 2024

This is an initial, abstract-level pass across a handful of queries; if you want, we can go deeper into how different assays (IHC vs mass spec vs qPCR) drive apparently different conclusions about which cell types express spike and for how long.