The Potential of AAV-Mediated Gene Targeting for Gene and Cell Therapy Applications

Abstract

Modern genomics offers unprecedented prospects for both discovery science and human health. Major health impacts will be achieved through gene and cell therapy approaches, individually and in combination, but the technologies required are only just beginning to come of age. The three critical challenges for the gene therapy field are improving the efficiency with which target cell populations can be gene-modified, effecting genetic modifications that faithfully recapitulate physiological gene expression and control and avoidance of inadvertent damage to the genome with the associated risk of neoplasia. Fully addressing these challenges requires the development of precise, specific and highly efficient genome editing technologies. Much justified fanfare has accompanied the development of user-designed nucleases, but the therapeutic potential of this evolving technology remains constrained by the challenges associated with delivery and is highly disease and target cell type specific. This review focuses on the synergistic therapeutic potential of adeno-associated virus (AAV)-mediated gene targeting technology, which simultaneously addresses the challenges of efficient delivery and precise genome editing.