It is becoming clear that vectors based upon adeno-associated virus (AAV) are the vectors of choice for certain gene therapy applications such as muscle delivery. The utilization of AAV vectors in such protocols is based on the advantageous properties of AAV. These properties include lack of pathogenicity and pathology, ease of preparation and purification, long term expression in many tissues including the muscle, and lack of a detrimental cell-mediated immune response.
AAV serotype 2 (AAV2) is the best studied of the AAV isolates. Over the past decade, inroads have been made in the evaluation of the tissue tropism of alternative AAV serotypes. These studies have shown that distinct AAV serotypes may be better suited for particular applications. In this regard, serotypes 1, 6 and 7 are the most promising for delivery to skeletal muscle. For example, as compared with AAV2, AAV1 can be administered at lower dosages (i.e., fewer particles) and can express the transgene at earlier time points and at higher levels of expression.
The purification schemes for AAV2 are well defined. Less streamlined are the purification parameters for some of the other AAV serotypes. It would be desirable to engineer a variant of AAV2 that exhibits advantageous properties, such as the enhanced muscle tropism of AAV1, 6 and 7, but still maintains its ease of purification. Increasing the range of available AAV vectors will also address additional concerns related to re-administration and immune responses.
Accordingly, it would be desirable to have available a broader array of AAV vectors.