2017 was a significant year for gene therapy: the first treatments using genetically engineered T cells expressing the chimeric antigen receptor (CAR-T) for cancer treatment (Kymriah and Yescarta) were approved by the FDA and a ground-breaking skin graft was performed in Germany using autologous transgenic keratinocytes. In both mentioned approaches, cells are genetically engineered using integrating viral vectors outside the patient body, ex vivo, where safety risks, like insertional mutagenesis, are easier to control.

To address the safety concerns relating to in vivo human therapeutic use, researchers are now turning to alternative physical delivery approaches, such as electroporation of nonintegrating plasmid vectors. The approach is called gene electrotransfer (GET) and both groups, participating in the project, were among the pioneers in its development. GET is now considered one of the most efficient non-viral gene therapy approaches for localised in vivo transfection of different tissues.

The most easily accessible tissue for GET is skin, which is our biggest immune organ. Therefore, it is a particularly attractive organ for immune based gene therapy approaches, like DNA vaccination. However, the immune cells were proven hard to transfect in the past. In the joint project, our aim will be to evaluate and increase the transfection efficiency of skin-resident immune cells. Both groups already have experience in skin transfection.

We expect that joint collaboration will help to improve the transfection of skin, with the special focus being on the selective transfection of different populations of immune cells. If successful, the adapted protocol could be implemented for in vivo generation of tumor antigens-expressing dendritic cells or CAR-expressing T-cells or even to achieve stable transgene expression using CRISPR technology.