Médecine moléculaire et génétique

Progress and Problems with Viral Vectors for Delivery of Talens

Abstract

Thorsten Bergmann, Eric Schulz and Anja Ehrhardt

It has long been envisaged that gene disruption or gene correction in affected target cells can be efficiently conducted in vitro and in vivo and over the recent years several tools for achieving this goal were developed. Designer nucleases such as zinc finger nucleases (ZFNs) were extensively explored and more recently transcription activator-like effector nucleases (TALENs) were introduced for sequence-specific genome engineering in the mammalian genome. ZFNs and TALENs are fusion proteins containing a customized DNA-binding motif for sequence-specific DNA binding linked to a nuclease for introduction of double-stranded DNA breaks. Both systems were explored in mammalian cells using non-viral and viral delivery methods. Herein, we will provide a state-ofthe- art overview of available virus-based delivery systems for sufficient expression of functional TALENs. We will cover the molecular design of recombinant viruses containing TALEN expression cassettes and we will mention advantages and disadvantages of the respective systems. Although the relevance of these viral vector systems for novel developments in molecular medicine and genome engineering need to be further evaluated, we believe that with further improvements these viral vectors for TALEN delivery will play an emerging role in bioengineering and for establishing novel therapeutic concepts.