Abstract

Targeted Genome Editing in IPSC - From Disease Modelling Towards Therapy

Toni Cathomen, Director, University Medical Center Freiburg

Targeted genome editing with designer nucleases has become increasingly popular. The most commonly used designer nuclease platforms are meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system. These powerful tools greatly facilitate the generation of plant and animal models for basic research, and harbor an enormous potential for applications in biotechnology and regenerative medicine. However, the application of designer nuclease technology in humans requires special considerations. Given that off-target cleavage activity of customized nucleases can potentially induce genotoxic side-effects, including the transformation of the target cell type, particular attention has to be paid to the specificity of designer nucleases. In my talk I will present data on preclinical applications of designer nucleases, highlight parameters that affect specificity of these nucleases, and end with a personal view on what aspects should be contemplated before moving into the clinic.