# 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.