Adeno-associated viral vectors: background and technical aspects

Abstract

There are several obstacles that prevent the successful clinical application of gene therapy. Some of these challenges are unique to the particular disease and organ that is being targeted. Desirable characteristics of approaches aimed at delivery of a therapeutic gene to the kidney ideally will require a vector that is safe, that efficiently transduces nondividing cells, and that can lead to long-term gene expression. Viral vectors that are derived from the small replication-deficient parvovirus, adeno-associated virus, offer many potential advantages. The wild-type virus is nonpathogenic and can site specifically integrate at a single location on chromosome 19, a process that offers the hope that this characteristic could be engineered into recombinant vectors as well. Recombinant adeno-associated virus can also efficiently integrate into the host genome, can transduce nondividing cells, and does not induce an immune response which destroys the transduced cells. Efforts focused both on gaining a more complete understanding of the virus life cycle as well on the efficient production of high-titer virus should bring this vector closer to clinical application.