Researchers at The Ottawa Hospital and the University of Ottawa have discovered an 18-digit code that allows proteins to attach to exosomes – tiny, tiny bits of cells that travel throughout the body and transmit biochemical signals. The discovery, published in Advances in Sciencehas significant implications for the growing field of exosome therapy, which seeks to harness exosomes to deliver drugs for various diseases.
“Proteins are the body’s home medicine, but they don’t necessarily travel well in the body,” said Dr. Michael Rudnicki, senior author of the study and Director of the Regenerative Medicine Program at The Ottawa Hospital and professor at the University of Ottawa.
This discovery allows us to harness exosomes to carry any protein throughout the body. It opens the door to a whole new field of drug development.”
Dr. Michael Rudnicki, Senior Author and Director, Regenerative Medicine Program, The Ottawa Hospital
Dr Rudnicki and his team discovered the exosome-targeting zip code within a protein called Wnt7a, which plays a critical role in growth, development, regeneration and cancer. First, they showed that Wnt7a can attach to exosomes. They then deleted different parts of the Wnt7a protein until they found the smallest part responsible for targeting exosomes. They named this segment, which consists of 18 amino acids, the Exosome Binding Peptide (EBP). They then discovered that EBP binds to proteins called Coatomers in exosomes, and that EBP could be used to target any protein in exosomes.
“Researchers have been trying for years to turn Wnt7a into a drug for muscle regeneration, but it is very difficult to deliver Wnt7a throughout the body, as it is covered by fatty molecules that do not mix well with body fluid,” said the first author Dr. Uxia Gurriaran-Rodriguez, a former postdoctoral fellow in the group of Dr. Michael Rudnicki, who now works at the Center for Collaborative Research in the Life Sciences. (CIC bioGUNE) in Spain. “Now that we know how Wnt7a binds to exosomes, we have solved this problem and can now accelerate the development of drugs for devastating diseases such as Duchenne muscular dystrophy.”
Exosomes have become an important area of research for both academic laboratories and biopharmaceutical companies, with DelveInsight predicting “enormous” growth in the field. The Ottawa Hospital, along with the University of Ottawa and other partners, has become a leader in combining exosomes with proteins, RNA and other biomolecules to develop new therapies. The Ottawa Hospital Biotherapeutics Manufacturing Center will continue to play a key role in translating this promising part of the life science innovation ecosystem to the benefit of patients.
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Journal Reference:
Gurriaran-Rodriguez, U., et al. (2024) Identification of the Wnt signal peptide that directs secretion into extracellular vesicles. ScienceAdvances. doi.org/10.1126/sciadv.ado5914.
