Extracellular Vesicles as mediators for intracellular delivery of macromolecules using engineered cells

Extracellular vesicles (EVs) have emerged as novel vectors for the delivery of macromolecular drugs. However, EVs have undesirable features, such as a short half-life in circulation and limited targeting capabilities.

I, therefore, aim to develop an EV cell-based therapy that produces engineered EVs for delivery of macromolecular cargo locally where they are needed.

To achieve this, I will utilise the Synthetic Notch (SN) system to engineer cells that upon exposure to a specific antigen start to secrete therapeutic EVs.

The SN EV cells will overcome the delivery issues that many macromolecular drugs are associated with and finally fulfil the capacity of RNAi, mRNA and protein therapeutics.

Within the project the SN EV platform will be developed to deliver different macromolecular cargos; shRNA that will be tested in a pancreas cancer model and CRISPR/Cas9 that will be evaluated to treat Duchenne muscular dystrophy (DMD), a terminal genetic disease affecting 1 out of 3500 boys.I am a resident in Clinical Immunology and Transfusion Medicine and would continue in the clinic 50% and work with this project 50%, leading the project and planning experiments.

One PhD-student and one PostDoc (funded from another grant) will furthermore be involved and perform experiments.

The combination of cell and EV therapy will be a big leap forward for both fields and can lead to novel patient-specific and highly efficient treatments that would benefit patient cohorts without curable treatments.