Professor for Somatic Gene Therapy
Vice-Director, Institute for Regenerative Medicine
Research Focus: Development of viral vector- and gene editing-based strategies targeting different monogenic disorders. In general, low availability of the primary patient material is a critical constraint for the early-stage development of gene therapy approaches in rare diseases. Currently, our portfolio of targeted disorders includes rare primary immune-deficiencies and neurodegenerative diseases. Disease modelling with induced pluripotent stem cells (iPSCs) represents a physiologically relevant alternative to primary patient material, with a virtually unlimited source. According to the genetic background of the diseases and the targeted tissue, we employ gene therapy approaches based on either viral vectors (lentiviral vectors and AVV) or gene editing (CRISPR/Cas). Thanks to the ability to differentiate toward specific lineages, patient-derived iPSC allow for the initial testing of the outcomes of the gene therapy approaches by assessment of phenotypic rescue of the functionally impaired target cells. iPSC in vitro models provide an important platform for our initial screenings before proceeding with in vivo studies in animal models for subsequent studies of efficacy and safety in a complex organism. Additionally, iPSC culture makes an attractive source of disease-relevant genotype and phenotype for complex studies on interaction between different cell types, which may prove useful for treating genetic disorders in the future.
Methods: Differentiation of iPSC to hematopoietic stem cells, macrophages, neuronal cells, CRISPR editing, lentivirus and AAV based gene therapy.
Keywords: CRISPR/Cas genome editing, viral gene therapy, lentivirus, AAV
Topics: Gene Therapy, Disease Modelling, Rare Diseases, Immunology, Neurodegeneration.
Publications: https://pubmed.ncbi.nlm.nih.gov/Website: https://www.irem.uzh.ch/en.html