The adeno-associated virus vector for orthopaedic gene therapy.

During the last decade researchers working with recombinant adeno-associated virus have shown the use of this vector for efficient and long-term gene transfer in various tissues including lung, muscle, brain, spinal cord, retina, and liver. In 1999 the first results documenting the use of this vector in transducing joint cells were published. Additional advantages of recombinant adeno-associated virus for in vivo gene therapy are: (1) its ability to transduce nondividing cells; (2) site-specific integration into the host genome; (3) high viral titer (> 10(13)/mL); and (4) the vector is not cytotoxic and does not provoke a significant immune response. Most important, several groups have documented the ability to deliver sustained transgene expression in an immunocompetent host for more than 1 year, and that curative levels of gene product (factor IX), from one injection is sustained long-term in a large animal (hemophilia B dog). Comparable results have not been achieved with any other vector to date. As a result of this work the first Phase I clinical trials using recombinant adeno-associated virus are under way for cystic fibrosis. The history of the recombinant adeno-associated virus vector and its future promise for orthopaedic gene therapies are described. The goal of the current review is to provide the reader with an understanding of the advantages and disadvantages of this vector for treatment of musculoskeletal diseases. Additional information concerning recombinant adeno-associated virus can be obtained in more general reviews.