Engineering extracellular vesicles (exosomes) for nucleic acid delivery: exoASO‑STAT6® exosomes as a case study

Extracellular vesicles (EVs), including exosomes, can transport a range of different molecular cargo to target cells, making them a promising therapeutic modality. EVs can be engineered to load molecules on their surface or inside the lumen through identified scaffold proteins, namely PTGFRN and BASP-1, respectively. Using these scaffold proteins, the engEx® cell engineering technology, acquired by Lonza from Codiak BioSciences, has been developed to engineer exosome therapeutics including exoSTING®, exoASO-STAT6®, and exoIL-12™ exosomes. These have been tested in in vivo tumor models and subsequently evaluated in Phase 1 clinical trials. In particular, exoASO-STAT6 exosomes enable nucleic acid delivery to the tumor microenvironment and provides the ability to reprogram it. The Xcite® EV platform technology, developed based on the engEx technology, facilitates the generation of engineered EVs and is now available to the broader scientific community via Lonza’s service offerings.