Lipid nanoparticles, called LNPs, are tiny bubbles that can carry messenger RNA (mRNA) into cells. They helped deliver the COVID‑19 vaccines to billions of people.
Scientists now want to use LNPs for many other medicines, such as cancer drugs, treatments for inflammation, and tools that edit faulty genes (CRISPR).
One big problem is that LNPs do not join with cell walls as well inside a living body as they do in the lab. This makes the therapy less effective.
Easy Fix Using Three Amino Acids
A team at Biohub discovered a very simple fix. They added three everyday amino acids—methionine, arginine, and serine—to the LNP mixture. This tiny change made the mRNA enter cells up to 20 times better and lifted CRISPR editing from about 25 % to almost 90 % after just one dose.
“Future medicines that use mRNA or gene editing need LNPs to get inside cells,” said Shana Kelley, head of Biohub’s bioengineering program. “Our trick could help any LNP‑based drug being made today.”
Why Cells Were Holding Back
Most researchers tried to redesign the nanoparticles themselves, testing hundreds of new fats and even using artificial intelligence. Yet the results in patients stayed modest.
Biohub’s scientists asked a different question: Maybe the cells themselves were the barrier. They grew cells in a fluid that looks more like human blood. In that setting, the cells took up only half to a fifth of the LNPs compared with standard lab conditions.
They found that the cells had less activity in pathways that use amino acids. In other words, the cells were “starved” for certain nutrients, so they were slower to grab the nanoparticle bubbles.
Adding the Amino Acids Makes a Big Difference
When the three amino acids were given together with the LNPs, protein made from the delivered mRNA jumped 5‑ to 20‑fold in many cell types. The boost was seen in petri‑dish tests and in live animals.
The improvement worked no matter how the LNPs were given—by injection into muscle, into the lungs, or directly into the bloodstream. It also worked with different nanoparticle designs and with both mRNA and CRISPR cargo.
Animal Tests Show Stunning Results
In mice with a severe liver injury caused by an overdose of acetaminophen, the mRNA that makes growth hormone saved only 33 % of the animals when used alone. With the amino‑acid mix, every mouse survived, protein levels rose almost nine times, and liver damage fell to almost normal.
Another experiment sent CRISPR tools to mouse lungs. Without the supplement, only 20‑30 % of the genes were edited. With the amino acids, editing rose to 85‑90 % after a single dose—an amount that could be useful for diseases like cystic fibrosis.
Easy Path to Real‑World Use
The three amino acids are already made in huge quantities and are considered safe. Adding them to existing LNP medicines could be as simple as mixing an extra powder into the final drug.
Instead of redesigning the nanoparticle, the researchers focused on the cell’s own chemistry. This practical idea may finally let mRNA and gene‑editing therapies reach their full promise.