Biophysical characterization of adeno-associated virus capsid through the viral transduction life cycle

Adeno-associated virus (AAV) vectors have emerged as the leading delivery platforms for gene therapy. Throughout the life cycle of the virions, the capsid vector carries out diverse functions, ranging from cell surface receptor engagement, cellular entry, endosomal escape, nuclear import to new particle packaging, and assembly. Each of these steps is mediated by exquisite structure features of the viral capsid and its interaction with viral genome, Rep proteins, and cellular organelle and apparatus. In this brief review, we provide an overview of results from over a decade of extensive biophysical studies of the capsid employing various techniques. The remaining unaddressed questions and perspective are also discussed. The detailed understanding of the structure and function interplay would provide insight to the strategy for improving the efficacy and safety of the viral vectors.