Stimulation of AAV Gene Editing via DSB Repair

Abstract

Recent advancements in mammalian genome editing technologies have demonstrated precise genetic manipulations at the chromosomal level at efficiencies relevant for disease therapy. In fact, zinc-finger nucleases (ZFNs) that induce deletions in the HIV CCR5 receptor in patient T cells ex vivo have demonstrated promise upon treated cell infusion in the clinic. In these applications, adenoviral delivery vectors were employed however; there is growing popularity for the use of adeno-associated virus (AAV) gene delivery which has been used in over 100 clinical trials without any vector-related toxicity. This review chapter summarizes the development of AAV for clinical gene therapy, the early observations of AAV gene targeting, and the current status of AAV vectors for gene editing via site specific DNA double strand break repair. In addition, the remaining obstacles towards the combination of AAV vectorology and site-specific endonucleases for genetic engineering are discussed.