Gene and cell therapy

Electroporation can be used to enhance the delivery of therapeutic nucleic acids (DNA, RNA) into various types of cells for gene therapy. The advantage of electroporation is that it is a nonviral delivery approach with an improved safety profile compared to conventional viral vectors. Delivery of nucleic acids with electroporation is termed gene electrotransfer (GET). We maintain active research in GET of the skin and skeletal muscle for development of DNA vaccines with applications in both prophylactic vaccination and therapeutic immunization strategies for cancer and infectious diseases. More recently, we have been investigating the potential of GET for gene therapy of cardiac muscle. One of the most ambitious frontiers in regenerative medicine is the repair of damaged heart muscle following myocardial infarction. For decades, the adult human heart was considered incapable of significant regeneration. In collaboration with King's College London, University Medical Centre Ljubljana, and Institute of Oncology Ljubljana, we are involved in the preclinical development of a gene therapy approach based on reversible electroporation to promote growth and proliferation of cardiomyocytes (cardiac muscle cells). Our research combines theoretical modeling of electric field distribution in cardiac tissue, experimental optimization of electroporation protocols on isolated cardiomyocytes and cardiac tissue slices in laboratory environment, and evaluation of therapeutic gene delivery in preclinical models. The ultimate goal is to develop clinically viable protocols for local delivery of therapeutic genes that could stimulate the heart's regenerative capacity and enable treatment of hearts suffering from ischemic injury.

Beyond gene delivery, we are exploring whether electroporation can be used to enhance the retention of therapeutic stem cells in cardiac tissue, which would be particularly beneficial for patients with heart failure receiving cell therapy. In collaboration with University Medical Centre Ljubljana, we are investigating whether controlled electroporation may improve retention of transplanted cells in the host tissue. In another direction, we are investigating the mechanisms of electroporation and gene electrotransfer in lymphocytes and natural killer (NK) cells in the context of CAR-T and CAR-NK therapy development. Cell-based immunotherapies, particularly chimeric antigen receptor (CAR) therapies, represent one of the most promising advances in cancer treatment and require efficient transfection of immune cells with genetic constructs encoding the chimeric receptors. Our work focuses on optimizing electroporation protocols to achieve high transfection efficiency while maintaining cell viability and function, which is critical for the therapeutic efficacy of these engineered immune cells.