Bence Gyorgy, MD, PhD
Head of Clinical Translation, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland
Gene therapy is revolutionizing medicine and previously untreated diseases become manageable. The market approval of several gene therapy drugs sets the stage for this treatment modality to reach broader patient populations. These traditional gene therapy applications rely on supplying the normal coding sequence of a gene by means of viral vectors. With the advent of genome editing it is possible to therapeutically intervene at the genomic DNA level and this opens a door towards the development of next generation therapeutics. The field has experienced an unprecedented acceleration after the discovery of the CRISPR/Cas9 system (clustered regularly interspaced short palindromic repeats) which allows researchers to target virtually any site in the genome using a short RNA motif (guide RNA, gRNA). Gene editing is advancing fast into clinical applications and recent tools can now target mutations with single base precision. The idea that there is a potential to correct the underlying genetic problem is unprecedented in biomedicine and the fact that this strategy can reasonably reach the clinic within 5-6 years provides an exceptional opportunity. Adeno-associated viral vectors (AAVs) emerged as safe and efficient delivery vectors to non-dividing cells in vivo. They are currently the gold standard delivery tools for the retina or the central nervous system. Although gene editing components need only temporary expression, AAV vectors are being utilized to deliver these components into target cells in vivo. AAV-delivery of CRISPR components have unique challenges, such durable expression with potential long-term off-target effects and AAV vector integration. On this talk, we will discuss the promises and challenges of AAV-delivery of CRISPR and next-generation precision gene editing components.