CRISPR genome engineering and viral gene delivery: A case of mutual attraction

The adaptation of the CRISPR/Cas9 DNA engineering machinery for mammalian cells has revolutionized our approaches to low‐ or high‐throughput genome annotation and paved the way for conceptually novel therapeutic strategies. A large part of the attraction of CRISPR stems from the small size of its two core components – Cas9 and gRNA – and hence its compatibility with virtually any available viral vector delivery system. As a result, over the past two years, four major classes of viral vectors have already been engineered and applied as CRISPR delivery tools – retroviruses, lentiviruses, adenoviruses, and adeno‐associated viruses (AAVs). The juxtaposition of these two technologies reflects a case of tremendous mutual attraction and holds unprecedented promises for biology and medicine. Here, we provide an overview of the state‐of‐the‐art of this rapidly emerging field, from a comparative description of the principal vector designs, to a synopsis of some of the most exciting applications that were reported to date, including the use of viral CRISPR vectors for genome‐wide loss‐of‐function screens, multiplexed gene editing or disease modeling in animals. Once specificity and safety have been improved further, viral vector‐mediated in vitro/in vivo CRISPR delivery and expression promise to radically transform basic and applied biomedical research.