BBB seminar: Beat Thöny

Beat Thöny
Division of Metabolism, University Children's Hospital Zurich and Neuroscience Center Zurich, Switzerland

Phenylketonuria (PKU) and urea cycle defects (primarily ornithine transcarbamylase (OTC) deficiency) are paradigms for monogenetic (metabolic) liver disorders and targets for gene therapy. While PKU is considered an ideal “test system” for experimental gene therapy for the liver due to its excellent mouse model and the easy to analyze and well-defined therapeutic end-point, i.e. blood phenylalanine concentration, assessment of ureagenesis is more challenging and needs sophisticated methods for quantification. Life-long treatment of mouse models for PKU and OTC deficiency was achieved using adeno-associated virus (AAV) vector-based gene addition and gene editing (Villiger et al., 2018), as well as non-viral, naked DNA, also called minicircle-vector gene therapy. I will summarize experience from our laboratory regarding gene therapeutic attempts to correct liver defects in experimental animals and discuss implications for human gene therapy.

Reference:

Villiger L, Grisch-Chan HM, Lindsay H, et al. Treatment of a metabolic liver disease by in vivo genome base editing in adult mice. Nat Med. 2018, 24:1519-25.

Chairperson: Aurora Martinez, Department of Biomedicine