Science1 publisher2 min readPublished
Where mRNA nanoparticles enter the gut steers which organs they reach in mice
Georgia Tech and Emory researchers found the gut site where a lipid-nanoparticle mRNA dose lands, cheek to rectum, changes which organs it reaches in mice. That turns the delivery site into a tool for aiming oral vaccines at lymph nodes or GLP-1 therapy at the pancreas.
The Scientist · Science desk
What happened
- Standard LNP delivery, into a vein or under the skin, concentrates the particles in the liver, lungs and spleen and brings the side effects that cap the dose.
- Sending the particles through the gut instead reduced their uptake in those organs in the mouse experiments.
- A dose placed in the cheek matched or improved a vaccine's immune response compared with a traditional injection.
- The results appear in the journal ACS Nano.
Compiled by The ScientistSomething wrong?How this is made
Why it matters
- capability Abramson's point is headroom: a drug limited by liver and lung toxicity could be dosed higher if the gut route keeps particles out of those organs.
- cost Ghanim says reaching a target directly could cut the dose a vaccine needs and lower the cost of making mRNA shots.
- constraint There is no oral product here, only a targeting principle; the delivery hardware for people, pills, patches and endoscopic injectors, is still in development.
The mice did not swallow a capsule. The team used microneedle injections to place the lipid nanoparticles at specific points along the GI tract, then tracked where the particles traveled afterward [7]. So the finding describes what the entry site does to distribution once the particle is already in the tissue. A swallowed dose is a different question. The study cannot say whether it would reach the same spot, or how much of it would survive the trip.
The clearest therapeutic test used the stomach. A GLP-1 message delivered there improved blood sugar regulation in the mice [8]. GLP-1 drugs are already used to treat obesity and diabetes [9]. "Here we show that oral delivery of mRNA wouldn't just enhance the patient experience compared to injections, but it also may enable improved or even completely new treatments," said Abramson, an assistant professor at Georgia Tech [14].
Safety is the claim with the most room to move. "We found that the LNP was completely safe at a very high dose when delivered via a gastric route of administration," said Abbas, a Ph.D. student in James Dahlman's lab at Emory [10]. The write-up reports which way things moved but not by how much; how much the immune response rose and how far blood sugar fell are not given. Whether the organ steering survives the move from a mouse gut to a human one is still open.
What to watch
- Whether the organ steering repeats in a species closer to people, not just mice.
- Which other GI sites and disease targets the team maps next.
- Whether an oral GLP-1 mRNA can match injectable GLP-1 drugs on glucose and weight.