Integrative approaches to enhance adeno-associated viral gene delivery

To meet the present and future challenges in achieving therapeutic in vivo gene delivery using adeno-associated virus (AAV), new innovations are required that integrate knowledge from disciplines ranging from biomaterials science, drug delivery, immunobiology, to tissue engineering. One of the foremost challenges remaining is in addressing pre-existing and therapy induced immune responses to AAV which significantly limit its therapeutic effect. In addition, functional correction of diseased tissues will depend on the ability of AAVs to retain activity after local or systemic administration and broadly distribute in target tissues. In this contribution to the Orations - New Horizons of the Journal of Controlled Release, I will introduce new concepts and potential strategies pursued by our lab and others to better understand and overcome these hurdles to effective AAV gene therapy. These multi-disciplinary approaches may open the door to the creation of precision gene therapies to treat heavily burdensome and often deadly diseases.