The flu virus-mimicking nanoparticles enter and release into a cell. A specialProtein on the nanoparticle's surface causes it to fusion with the endosomal membrane, allowing its messenger RNA cargo to escape into the host cell. The Chemie International Edition is a credit.
The University of California San Diego has developed a new and potentially more effective way to deliver messenger RNA into cells. Their approach involves packing mRNA inside nanoparticles that mimic the flu virus, which is a naturally efficient vehicle for delivering genetic material inside cells.
A paper about the new delivery nanoparticles is in the journal Angewandte Chemie International Edition.
The work addresses a major challenge in the field of drug delivery, getting large biological drug molecules safely into cells and protecting them from endosomes. These tiny bubbles inside the cell serve as barriers that trap and digest large Molecules that try to enter. Once they are inside the cell they need a way to escape the endosomes.
The amount of mRNA that actually gets released into cells and shows effect is very low because current delivery methods do not have very effective endosomal escape mechanisms. The majority of them are wasted when they are administered.
The efficient endosomal escape would be a game-changer. If you can get more mRNA into cells, this will allow you to take a lower dose of the vaccine, and this will reduce side effects. Delivery of small interferingRNA into cells could be improved by it.
Viruses do a good job of escaping. The hemagglutinin on the surface of the influenza A virus is activated by acid inside the endosome, which in turn causes the virus to attach to the endosomal membranes. The virus can release its genetic material into the cell without being destroyed.
The flu virus's ability to do this was mimicked by the team. The researchers genetically engineered the cells in the lab to express the hemagglutinin. They separated the cells from the membranes, broke them into small pieces, and coated them with a pre-packed messenger RNA molecule.
The finished product is a flu virus-like particle that can get into a cell, break out of the endosome, and free the messenger RNA to do its job.
The mice were tested. The nanoparticles were packed with the same type of material as the Cypridina luciferase. They were administered through the nose and then via injection. A significant amount of bioluminescence signal was found by the researchers after they imaged the noses of the mice. This was proof that the flu virus-like nanoparticles were able to deliver their contents into cells.
The researchers are testing their delivery system.
More information is available in the Angewandte Chemie International Edition. There is a DOI for 10.1002/anie.202113671.
The journal information is from the Angewandte Chemie International Edition.
Flu virus shells could improve delivery of mRNA into cells.
The document is copyrighted. Any fair dealing for the purpose of private study or research cannot be reproduced without written permission. The content is not intended to be used for anything other than information purposes.
