Researchers have found a way to regulate how easy it is to open and close a tiny protein cage, bringing the promise of controllable nanoscale drug delivery systems a step closer.
Due to COVID-19 everyone is now familiar with the idea of delivering mRNA to cells. This is one example of what many believe to be the future of therapeutics: Drugs will increasingly become large biological molecules such as RNA, DNA and proteins. These molecules offer the promise of more sophisticated, effective treatments often curative or preventative. However, these so-called biological macromolecules are often very fragile and easily broken down and deactivated. The challenge is how to protect them until they reach the site in the body where they are required. Putting them inside a protein cage is one possibility but protein cages are usually very stable meaning that it takes very harsh conditions to break them apart – such conditions would also destroy the therapeutic cargo. Recently a type of hollow, naturally occurring protein cage called ferritin has been discovered that actually breaks apart only in very mild conditions – simply a change in the concentration of salt. In the recently published work led by Mantu Kumar from the laboratory of Prof. Jonathan Heddle showed that changing a single amino acid in the protein could abolish the salt dependence while other changes had intermediate effects, raising the prospect that the conditions in which the cage opened could be fine-tuned. “It’s a useful piece of information, a part of the puzzle of how to fully control protein cages for drug delivery so that they go where we want and do what we want” said Prof. Heddle.
The work was carried out by the Bionanoscience and Biochemistry Laboratory, Malopolska Centre of Biotechnology, in collaboration with the Institute of Zoology and the Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University.
Read the Full article “A single residue can modulate nanocage assembly in salt dependent ferritin” published in RSC Nanoscale here: https://pubs.rsc.org/en/content/articlehtml/2021/nr/d1nr01632f
To find out more about our work visit the lab website: www.heddlelab.org