Adeno-associated virus (AAV) is a human parvovirus that was initially discovered as a contaminant in adenovirus preparations. AAV requires a helper virus, such as adenovirus, to mediate a productive infection (18). There are six known human virus serotypes, of which AAV-2 is the best studied. No known human disease is associated with AAV.
AAV vectors have a number of qualities that make them highly suitable for gene therapy. AAV vectors can effect transgene expression in nondividing cells. Also, although they also can be episomal, AAV can integrate into the infected cell's genome. This provides AAV vectors with the potential for effecting long-term transgene expression, even in successive generations of daughter cells (19-21). Finally, AAV vectors generally do not induce inflammatory responses or cytotoxic immune responses against infected cells (18,22-24).
However, like adenovirus vectors, injection of free AAV can elicit neutralizing antibodies that can mitigate the ability of subsequent injections to infect cells in vivo. Also, AAV can only accept transgenes of relatively small size (<5 kb). Large-scale production and purification of this vector is problematic, and this will require the development of improved packaging cell lines and chromatographic methods for vector purification (25,26).
Another unfavorable feature is that AAV vectors apparently do not infect lymphocytes or CLL cells efficiently, making it necessary to consider ex vivo transduction strategies that use AAV vectors at high concentration. Nonetheless, AAV vectors can efficiently transfer genes encoding antigens to cells in skin or muscle, allowing for their potential use as vaccines encoding tumor-associated antigens.
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