Journey to the Center of the Cell: Tracing the Path of AAV Transduction

As adeno-associated virus (AAV)-based gene therapies are being increasingly approved for use in humans, it is important that we understand vector–host interactions in detail. With the advances in genome-wide genetic screening tools, a clear picture of AAV–host interactions is beginning to emerge. Understanding these interactions can provide insights into the viral life cycle. Accordingly, novel strategies to circumvent the current limitations of AAV-based vectors may be explored. Here, we summarize our current understanding of the various stages in the journey of the vector from the cell surface to the nucleus and contextualize the roles of recently identified host factors. Despite being the ‘vector of choice’ for in vivo gene transfer, the process of cellular transduction of adeno-associated virus (AAV)-based vectors is not fully understood.The AAV transduction process can be dissected and studied in a stepwise manner, each step requiring the vector to interact with cellular host factors.The interaction of AAV-based vectors with specific host factors is critical for efficient transduction. The expression profiles of these host factors in different cell types determine vector tropism.Modulation of specific steps in cellular transduction may offer a valuable strategy to enhance gene therapy.