Therapeutic Protein Delivery from Light-activated Synthetic Cells

Membranes of cells are made of lipid bilayers. These lipid bilayers are hydrophobic, which make it difficult for macromolecules to pass through. This inability to gain access to the cell interior remains a major obstacle in the cellular delivery of therapeutic macromolecules, such as proteins. Cell-penetrating peptides (CPPs) have been developed to provide high delivery yield, low toxicity for the delivery of macromolecules. However, CPPs do not allow targeting or controlled activation. This DPhil project will aim to use synthetic cells, lipid-bounded compartments that can express protein, under the control of light-activated DNA to produce therapeutic proteins conjugated to CPP. This will allow the delivery of these therapeutic proteins into neighbouring mammalian cells, using the CPP as the transporter. Light-activation will give both controllability and targeting of cellular delivery. This method will be explored to study cellular models and as a potential method of drug delivery.