American engineers have designed a new type of nanoparticles that can be used in the lungs, where it can deliver messenger RNA (mRNA) encoding useful proteins. With further development, these particles can provide inhalable treatment methods for cystic fibrosis and other lung diseases. The study was published on March 30th in Nature Biotechnology. Daniel Anderson, professor of chemical engineering Department of MIT, said that this was the first time to prove that RNA was efficiently delivered in the lungs of mice. Researchers hope that it can be used to treat or repair a range of genetic diseases, including cystic fibrosis. In a study on mice, Anderson and his colleagues used these particles to transmit mRNA encoding the CRISPR/Cas9 component, which may open the door to designing therapeutic nanoparticles that can cut off and replace pathogenic genes. In the new study, researchers set out to develop lipid nanoparticles that can target the lungs. These particles are composed of two parts of molecules: a positively charged head base and a long lipid tail. The positive charge of the head base facilitates the interaction between particles and negatively charged mRNA, and also helps mRNA escape from the cell structure that engulfs particles. Meanwhile, the lipid tail structure helps particles pass through the cell membrane. Researchers have proposed 10 different chemical structures and 72 different head bases for lipid tails. By screening different combinations of these structures in mouse experiments, researchers were able to identify the structures most likely to reach the lungs. Research has shown that these particles can be used to transmit mRNA encoding CRISPR/Cas9 components, which aim to cut off the stop signal encoded into animal lung cells. When the stop signal is removed, the fluorescent protein gene will be turned on. Measuring this fluorescence signal enables researchers to determine the percentage of cells that successfully express mRNA. Researchers found that after one dose of mRNA, approximately 40% of lung epithelial cells were transfected, with two doses exceeding 50% and three doses reaching 60%. The most important target for the treatment of lung diseases is two types of epithelial cells - rod cells and ciliated cells, each of which is transfected at a rate of about 15%. New particles will also rapidly decompose, allowing them to be cleared from the lungs within a few days and reducing the risk of inflammation. If repeated doses are required, the particles can also be delivered multiple times to the same patient. The team is currently working to make the nanoparticles more stable so that they can be inhaled using an atomizer.