A quiet revolution is underway in modern medicine. Drug development aims to move from disease management to disease correction through RNA and gene editing therapies. However, safely and precisely delivering these therapies to the appropriate cells remains a major hurdle, especially in hard-to-target organs such as the brain and kidney.
Now, researchers led by a team at the University of Ottawa Faculty of Medicine have provided very convincing evidence that an elegant, natural solution resides in ultra-tiny bubble-like structures called small extracellular vesicles (sEVs). Refined over millions of years of evolution, these metabolic messengers carry RNA (nucleic acids, a chemical relative of DNA) and other molecules between cells.
In short, the research team’s new findings show that not all sEVs are the same. The cell of origin for sEVs determines where they migrate, and specific vesicles naturally target specific tissues within the body.
This discovery could unlock powerful new strategies to piggyback on these nanometer-scale particles to precisely and effectively deliver next-generation treatments.
Rethinking drug delivery
Dr. Derrick Givings, senior author of this groundbreaking study published in the journal cell biomaterialan international research team (including scientists from Brazil and the United States) says it was inspired by biology.
“Our approach was to learn from and collaborate with nature to find sEVs that can be delivered to tissues and cells where the most attractive targets for siRNA therapy reside,” he said, referring to powerful tools to suppress the expression of specific genes. “And identifying targets that have a high patient population and a high need.”
This is important because over the past decade there has been great excitement about small extracellular vesicles and their potential as drug delivery vehicles. However, so far we cannot say that it has been completely successful as the overall approach may be flawed. Global companies invested heavily in advancing this technology, but struggled to achieve success because they assumed that one type of sEV would work universally throughout the body.
Dr. Givings argues that this approach overlooks a fundamental principle in biology that communication between cells is highly specific. He says the fact that extracellular vesicle communication is highly targeted and regulated is “not surprising if we consider sEVs as biological communication devices.”
Rather than try to force a one-size-fits-all solution, his research team chose a different path. The interdisciplinary collaborators investigated how sEVs behave naturally and selected the best sEVs to reach specific tissues of interest.
Here’s how Dr. Givings describes the targeted approach: “sEVs carry specific messages to specific cells. If your house burns down, you don’t call the heart surgeon or the mechanic. If your computer crashes, you don’t call the plumber.”
Precise movement: Targets the kidneys and brain
This common sense strategy paid off. The research team identified an sEV that, when injected into the bloodstream, can deliver siRNA directly to the kidney and reduce disease symptoms in a mouse model of chronic kidney disease.
Importantly, they also found that when sEVs were administered directly into the central nervous system, they could successfully deliver therapy to the brain and improve outcomes in models of neurodegenerative diseases.
The research team systematically demonstrated similar success in larger animal models, with results that scaled predictably based on body size and were not substantially altered by species-specific biological differences. This evidence suggests that the researchers’ approach could be applied to human treatments in the future.
Scale up to improve clinical efficacy
The research team’s work builds on decades of exciting advances in siRNA therapeutics. siRNA therapeutics belong to a class of gene silencing drugs that utilize small interfering RNA molecules. Dr. Givings said: “siRNA is an incredible therapeutic agent…a single dose…can block the expression of disease-causing genes for six months.”
There are still various hurdles to clear. Producing sEVs at scale and improving the duration of siRNA therapy in the body is probably the main challenge for the global scientific community. But Dr. Givings is optimistic. He and his team are currently seeking partners to move this technology into clinical trials, with a particular focus on severe kidney diseases for which there are currently limited treatment options.
“We have collected a lot of data showing that sEVs are an effective, safe and scalable delivery vehicle, and we hope to persuade investors and industry partners to work with us to advance these towards clinical trials. Or, we hope to find physicians who will collaborate with us to advance these into clinical trials in academia,” said Dr. Givings, professor in the Department of Cellular and Molecular Medicine and vice president of research support and infrastructure at Ottawa.
He is particularly bullish about its potential use as a treatment for chronic kidney disease, which is caused by genetic mutations in the APOL1 gene.. “There are so many patients who often progress to the point where they need a transplant, and some people die from the disease.”
Ottawa’s ecosystem leadership in a rapidly changing sector
The newly published research led by Dr. Givings is one of many impactful collaborations focused on extracellular vesicles in Ottawa’s broader research community. Dr. Dylan Berger is a national and international leader in a growing field, to name a few notable researchers in this field. John Bell and Carolina Ilkow are leveraging their world-leading expertise to develop EVs for cancer treatment.
Studying extracellular vesicles is challenging because they are too small to be seen with most microscopes. But Dr. Givings says the field is uniquely exciting for medical researchers who are studying the mechanisms of long-distance cell communication and how to better treat a host of complex diseases.
“It’s like discovering that cells are using new media like the phone and TikTok to communicate, not just face-to-face conversations,” he says. “So we’re discovering what information and messages they’re sharing and how we can reprogram it to treat disease.”
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DOI: 10.1016/j.celbio.2026.100424
