We’ve all heard the phrase, “One man’s trash is another man’s treasure.” It turns out that what often holds true for the antique business also sometimes holds true for biotech. Let’s show how.

There are these teeny tiny things each of our cells secrete called exosomes. (Stay with us.) The term exosome derives from the Greek words for “external” and “body.” They’re only about one one-hundredth the size of a typical human cell. They’re microscopic parcels secreted from cells and filled with cellular leftovers— RNA, proteins, and other remnants of metabolic processes. Microbiologists first discovered them in the 1980s. Initially, the scientists thought exosomes were a kind of cellular trash bag—providing a way to eliminate the molecules a cell no longer needed. In the past decade, it’s become increasingly clear that exosomes and what they carry play a role in intercellular signaling by delivering their contents to recipient cells. These tiny vesicles shuttle proteins and genetic information between cells, acting as molecular mail carriers. Exosomes activate the immune system and are likely involved in other aspects of health and disease. Biopharma has turned its attention to figuring out how to use these miniscule containers to provide the means to deliver lifesaving medicines and aid in diagnosing diseases. They may eventually even act as stand-alone therapeutics.

The most apparent application of exosomes builds on their role as cellular couriers to deliver drugs to target tissues that are not easily reached by conventional methods, such as the brain, or to deliver drugs that do not usually enter cells, such as monoclonal antibodies or other protein therapeutics.

But how does a drug get inside these tiny vesicles, to begin with? First, exosomes come from cells grown in the lab. Once harvested, technicians load them with medicine in several ways. For instance, electroporation—jolting the exosome with pulses of electricity—creates a temporary permeability that allows the drug to enter the exosome.

Exosomes loaded up with medicine would then be injected into the patient. The exosomes find their target tissue based on proteins on that tissue’s surface. The exosome’s lipid membrane is so similar to the cell’s membrane that it can slip inside when they come into contact, delivering its content to the cell.

Exosomes display affinities for tissue based on location in the body from which they come. Researchers control targeting by harvesting exosomes from cells known to produce exosomes that deliver their goods to a specific tissue type. For example, exosomes from pancreas cells come equipped with “radar” that sends them to lung cells.

Codiak Biosciences (Cambridge, MA) is developing another approach to getting drugs where they need to go via exosome. Their proprietary platform enables them to engineer cells that produce both exosomes with specific contents and surface molecules that guide them. They have developed novel cancer therapeutic candidates. In 2022, Codiak released promising data from Phase 1 trials for these engineered exosome candidates; exoSTING™ and exoIL-12™. The results showcased a potential for a best-in-class profile, indicating significant tumor retention and precise delivery to cells of interest, which could potentially widen the therapeutic window. Currently, exoSTING™ and exoIL-12™ are in Phase 2 clinical trials.

Exosomal delivery makes a desirable option for drug makers with products that face significant delivery obstacles. These include RNA-based drugs that have struggled to achieve efficient delivery and biologic drugs too large to enter cells. Aruna Bio (Athens, GA) has developed exosomes that ferry drugs across the blood-brain barrier—another common stumbling block to drug delivery. For instance, AB126 by Aruna Bio is currently in Phase 2 clinical trials. It is both a therapeutic and a delivery vehicle with access to the central nervous system for treating a wide range of neurodegenerative diseases. Aruna Bio has plans to file its first Investigational New Drug (IND) application for AB126 in Q2 2023. This IND will be for stroke as a model indication for acute neurological conditions.

The therapeutic potential of exosomes goes beyond drug delivery. Regenerative medicine specialists at Temple University in Philadelphia demonstrated that injecting exosomes from embryonic stem cells can repair damaged cardiac muscle in a mouse heart attack model. Research at the University of New Mexico suggests that healthy cells near tumors produce exosomes that kill cancer but leave normal cells unharmed.

Biotech companies are following up on this basic science by developing exosome-based therapeutics. Codiak Biosciences is conducting Phase II clinical oncology studies of its treatments, exoSTING™ and exoIL-12™. Evox Therapeutics (Oxford, U.K.) is preparing to enter Phase I studies with an exosome-based therapy for lysosomal storage disorders. Research at Aruna Bio focuses on exosomes from neuronal stem cells that appear to reduce inflammation in the brains of mice and pigs and enhance their function. The company plans to develop these exosomes as therapies for stroke and amyotrophic lateral sclerosis (ALS). Finally, Celltex (Houston, TX) is also exploring the anti-inflammatory potential of neuronal stem cell-derived exosomes as a potential treatment for Alzheimer’s disease.

Exosomes may also enhance the diagnostic power of liquid biopsies. The idea is to capture exosomes based on tumor-specific surface markers or to collect exosomes from blood or urine samples and identify them as cancer-associated by examining the genetic material inside. Aptly named Exosome Diagnostics (Waltham, MA) has developed an exosome-based urine test for prostate cancer on the market. Biopharmaceutical companies are still in the early stages of understanding the power of the one-time cellular trash bag, but all the signs point to a nanoscale revolution led by exosomes.