The development of biological medicines has surged in recent years due to their enormous potential for treating a multitude of different diseases. Such medicines include nucleic acid- and protein-based therapeutics, which can be used to regulate the expression of genes aiming to prevent faulty proteins from being produced, to repair proteins or even to replace them. However, their widespread use is especially hampered by delivery issues. These medicines need to be encapsulated into nanocarriers to ensure their stability and efficient uptake into cells. To that end, many different approaches have been and are being developed, most of which end up in the liver making treatment of other organs a crucial challenge. In my lab we are developing strategies to engineer extracellular vesicles (EVs), tiny membranous vesicles, for their use as a drug delivery tool. Due to their natural origin, EVs are immune privileged and can cross biological barriers, including the blood-brain barrier. The DELIVER project aims to turn the liver into a “biofactory” to produce EVs that are then excreted into the circulation to reach other organs where they can release their therapeutic cargo. Within this project, the initial goals are to find the right instructions to achieve efficient production of EVs in the liver and to deliver these instructions safely and potently. Once this has been achieved, different engineering approaches will be explored with the aim of targeting these EVs to the central nervous system (CNS). Apart from that, to minimize systemic exposure the instructions will be delivered directly into the cerebrospinal fluid (CSF) to enhance local production of EVs in the CNS. The therapeutic potential of this approach will be evaluated in a Parkinson’s disease model. However, this DELIVER platform is intended to serve as a steppingstone for a variety of therapeutic applications involving disease-causing proteins since it is applicable to a wide range of biotherapeutics and thus treatment of various diseases.
