Characterization of adeno-associated virus binding to alginate and its controlled release

Abstract

Gene therapy is an increasingly explored research field with many viral vectors under study. Adeno-associated virus (AAV) is one of the more popular vectors, having already seen clinical success. While systemic or local injections are performed, more controlled means of delivery are being sought to localize treatment, reduce dosing and, minimize off-target effects. One commonly explored method is the use of hydrogels loaded with AAV placed at the site of interest. While investigating the use of alginate (a naturally occurring polysaccharide) we serendipitously discovered an interaction between the alginate itself and AAV. Through the use of atomic force microscopy (AFM) we were able to show that AAV binds to alginate and we quantified the force and frequency of the interaction. Furthermore, we have also shown that this interaction is serotype dependent, as it is not equal across different AAV serotypes. Finally, we showed that these differences in AAV serotype-alginate interactions correspondingly impact sustained release of the various serotypes from alginate hydrogels. This research offers novel insights into methods of controlled release of AAV.