Naïve exosomes can be engineered to load drugs into their lumen using two different technologies: passive drug loading and active drug loading. These “drugs” can include RNAs, proteins, and nucleic acids, as well as other payloads. Today, a growing number of companies are using engineered exosomes for therapeutic purposes and studies by these companies have confirmed that exosomes can effectively serve as carrier vehicles for several types of bioactive molecules. Several exosome therapeutics have also entered into clinical testing.
One of the pioneers in this field is Codiak BioSciences, a company that is using exosomes to ferry drugs into inaccessible parts of the body, such as the human brain.
Passive vs. Active Cargo Loading of Exosomes
Passive cargo-loading methods involve an incubation procedure to load bioactive agents into exosomes through sonication, electroporation, freeze-thaw cycles, and/or extrusion. Of course, one of the major disadvantage of these methods is that exosome structure can potentially be damaged during the membrane disruption process.
In contrast, active cargo-loading methods provide “parent” cells with means to load the proteins or nucleic acids into their exosomes during their biogenesis process. Meaning, the desired cargos get endogenously loaded by engineering parental cells to overexpress the desired proteins or nucleic acids of interest. These payloads are then naturally loaded into the lumen of their respective exosomes.
One such active cargo-loading method is to anchor the cargo onto the inner surfaces of exosomes via transgene expression in parental cells. For example, System Biosciences has developed specific peptide sequences for targeting interior exosomal membrane proteins, enabling a fusion protein to be loaded into exosomes for secretion.
Evox Therapeutics has developed a different loading method that involves making fusion proteins between protein and exosomal membrane proteins such as CD63, CD81, and syntenin. The problem with this approach is that the active pharmaceutical ingredient (API) remains attached to the exosomal membrane in the target cells, which can considerably limit the biological function in target cells.
ILIAS Biologics has developed a novel technology called “EXosomes for Protein Loading via Optically Reversible protein-protein interaction (EXPLOR)” to prevail over this limitation.
Other competitors have found solutions to achieve target-specific delivery of payloads without premature immune-mediated clearance. For example, System Biosciences has developed a method of exosome surface engineering post exosome isolation which can attach target-specific single-chain variable fragments (ScFv) to the outer membrane of exosomes. The company is now using this technology for the targeted delivery of payloads to HIV infected target cells in vivo.
The Evolution of Engineered Exosomes
Today, exosomes therapeutics are being developed by dozens of companies who are entering clinical trials with both passively and actively loaded exosome products. However, no exosome product has yet to be approved by the U.S. FDA.
Given this, the next few years will undoubtedly see dynamic change, growing numbers of clinical trials, and eventually, exosome commercialization. What other companies are commercializing actively and passively loaded exosome therapeutics? Mention them in the comments below.
To learn more about this rapidly expanding market, view the “The Global Exosome Market – Market Size, Forecast, Trials and Trends.”
