A Tiny Vesicle With Big Potential
Cambridge-based startup Codiak BioSciences made headlines last month with $40M launch funding and another $40M if their technology shows promise. So, what’s the big deal? A tiny little particle—once described as a cellular trash truck—called the exosome. First observed in the early 1980s, exosomes were originally thought to be a way for cells to get rid of molecules they no longer needed, dumping their contents into lysosomes. In the past decade, however, it has become increasingly clear that exosomes play a role in intercellular signaling because their routes and ability to transport cargo are much more than yesterday’s garbage. Let’s dive into the exosome and find out why their potential as vehicles for drug delivery and therapeutics are the talk of the town.
Term Of The Week: Exosome
The term exosome derives from Greek roots, literally translating to “external body.” They are in fact very small—about one one-hundredth the size of a typical human cell. These lipid-encased vesicles are secreted from human cells and contain cellular protein, DNA, and RNA.
Catching A Ride
Because of their established transportation procedures, exosomes may be able to deliver drugs to target cells. How? Exosomes can be collected from cells grown in the lab and “loaded up” with therapeutics via methods such as electroporation—pulsing the exosome with a short burst of electricity, creating temporary permeability which allows the drug to cross over its membrane. Loaded exosomes would then deliver the drug to the target cell based on target tissue surface proteins, similar to the way antibody therapeutics target specific tissues. Unlike antibodies, however, the exosome can actually enter the target cell because both the exosome and cell membrane are made up of lipid membranes. When like meets like, they fuse.
Exosomal delivery may help fill in the blanks for various types of established therapeutics unable to find their target market. The burgeoning class of RNA-based therapies still struggle to achieve efficient delivery mechanisms. Biologic drugs are too large to enter cells on their own and might be able to catch a creatively crafted ride on an exosome. A few studies have also suggested exosomes may be able to deliver drugs across the elusive blood-brain barrier—another common stumbling block.
Exosomes To The Rescue?
Earlier this year, researchers at Temple University (Philadelphia, PA) demonstrated that in a mouse model of heart attack, damaged cardiac muscle could be repaired by the injection of exosomes secreted by embryonic stem cells. Research at the University of New Mexico suggests that exosomes secreted by healthy cells near tumors can wipe out cancer cells—avoiding collateral damage to nearby tissues often seen in traditional therapies. This observation formed the basis of the startup Exovita Biosciences (Albuquerque, NM). Codiak BioSciences is also eyeing exosome-based cancer treatments as well as exosome-based regenerative medicine.
A Back Door Approach
Cancer cells secrete exosomes containing proteins and RNA specific to tumor antigens. The properties of these newly earmarked cancer-derived exosomes could be back channeled into a cancer vaccine if Exocyte Therapeutics (Singapore) fulfills their dream. Currently in preclinical studies, the putative vaccine works by collecting exosomes excreted by tumor cells, incubating those exosomes with white blood cells to stimulate their tumor-fighting activity, and injecting the activated blood cells back into the patient. Initial results suggest that exosomes are better at stimulating white blood cells than isolated tumor antigens, and in most cases much easier to collect from a patient than biopsy-derived antigens.
Exosomes are high-beaming with promise all over the map, but be sure to tune in next week to find out how these tiny vesicles with big potential might just revolutionize the fields of diagnostics.
Emily Burke, PhD has worked in biopharma for 20 years, gaining science writing experience at The Scripps Research Institute and Ionis Pharmaceuticals. As a Ph.D. molecular biologist, she is passionate about advancing the public’s understanding of science. In addition to being a self-proclaimed “science geek,” she is regularly asked to speak at international scientific meetings. When not teaching and writing the WEEKLY for Biotech Primer, Dr. Burke swims with her swim club and performs regularly on the improv circuit in San Diego.