Researchers at The Ottawa Hospital and the University of Ottawa have discovered an 18-digit code that allows proteins to attach themselves to exosomes - tiny pinched-off pieces of cells that travel around the body and deliver biochemical signals. The discovery, published in Science Advances, has major implications for the burgeoning field of exosome therapy, which seeks to harness exosomes to deliver drugs for various diseases.
"Proteins are the body's own home-made drugs, but they don't necessarily travel well around 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 deliver any protein throughout the body. It opens the door to a whole new field of drug development."
Dr. Rudnicki and his team discovered the exosome-targeting postal code or zip code within a protein called Wnt7a, which plays a critical role in development, growth, regeneration and cancer. First, they showed that Wnt7a can attach itself to exosomes. Then, they deleted various parts of the Wnt7a protein until they found the smallest part that was responsible for exosome-targeting. They called this part, which consists of 18 amino acids, the Exosome Binding Peptide (EBP). They then discovered that the EBP binds to proteins called Coatomers on exosomes, and that EBP could be used to target any protein to exosomes.
"Researchers have been trying for years to turn Wnt7a into a muscle regeneration drug, but it is very difficult to deliver Wnt7a throughout the body, since it is covered in fatty molecules that don't mix well with body fluid," said first author Dr. Uxia Gurriaran-Rodriguez, a former postdoctoral fellow in Dr. Michael Rudnicki's group, who is now working at the Center for Cooperative Research in Biosciences (CIC bioGUNE) in Spain. "Now that we know how Wnt7a attaches 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 a major area of research for both academic labs and biopharmaceutical companies, with DelveInsight predicting "tremendous" growth in the field . The Ottawa Hospital, together 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's Biotherapeutics Manufacturing Centre will continue to play a key role in translating this promising part of the life science innovation ecosystem for the benefit of patients.
Reference: Identification of the Wnt signal peptide that directs secretion on extracellular vesicles. Science Advances. Uxia Gurriaran-Rodriguez, David Datzkiw, Leandro G. Radusky, Marie Esper, Ehsan Javandoost, Fan Xiao, Hong Ming, Solomon Fisher, Alberto Marina, Yves De Repentigny, Rashmi Kothary, Mikel Azkargorta, Felix Elortza, Adriana L. Rojas, Luis Serrano, Aitor Hierro and Michael A. Rudnicki.
Funding and acknowledgements
This research was funded by Defeat Duchenne Canada, the Canadian Institutes of Health Research, the U.S. National Institutes for Health Research, the Frederick Banting and Charles Best Canada Graduate Scholarship Program, the Ontario Institute for Regenerative Medicine, the Stem Cell Network and Ministerio de Ciencia e Innovación (Spain). The lead research team is based in the Ottawa Hospital Research Institute (OHRI) Regenerative Medicine Program , which includes the Sprott Centre for Stem Cell Research and the Sinclair Centre for Regenerative Medicine. Collaborating institutions include the Barcelona Institute for Science and Technology (Centre for Genomic Regulation) and the Center for Cooperative Research in Biosciences (CIC bioGUNE). OHRI core facilities used in this research including Mass Spectrometry , Flow Cytometry and Bioinformatics . The researchers are inventors on a pending patent application held by OHRI that covers the use of the EBP to target proteins to exosomes. All researchers at OHRI follow a Responsible Innovation Framework for developing and commercializing innovations in a responsible way.
About The Ottawa Hospital
The Ottawa Hospital (TOH) is one of Canada's top learning and research hospitals where we are guided by our vision to provide the world-class and compassionate care we would all want for our loved ones. Our multi-campus hospital, affiliated with the University of Ottawa, is home to the Regional Trauma Centre and Cancer Centre, and to discoveries that are adopted globally. Backed by generous support from the community, we are focused on reshaping the future of health care to improve the health of our diverse population of patients from Eastern Ontario, Western Quebec, and Nunavut.
About the University of Ottawa
The University of Ottawa is home to over 50,000 students, faculty and staff, who live, work and study in both French and English. Our campus is a crossroads of cultures and ideas, where bold minds come together to inspire game-changing ideas. We are one of Canada's top 10 research universities—our professors and researchers explore new approaches to today's challenges. One of a handful of Canadian universities ranked among the top 200 in the world, we attract exceptional thinkers and welcome diverse perspectives from across the globe.
