AAV vectors hold great promise in treating a wide variety of diseases. In utilising sequences contained within the AAV genome to drive expression, as Targeted Genetics are working towards, the flexibility with respect to vector design is increased, which may allow the delivery of genes that might not ordinarily fit into a single AAV vector.
US patent 6,936,466, titled: "Transcriptionally Activated AAV Inverted Terminal Repeats (ITRs) for Use with Recombinant AAV Vectors," relates to technology that can increase the carrying capacity of AAV vectors, or produce vectors of a smaller size, which lead to metabolically activated recombinant vectors.
Targeted Genetics commented that the combined attributes of persistent expression and a good safety profile make AAV vectors the vector of choice for gene-transfer treatment for a wide variety of chronic disease and the development of viral vaccines.
AAVs have become a popular choice because it is stable enough to allow other formulation approaches to be used, in addition to the fact that it readily infects non-dividing cells (unlike retroviruses for example) and is not associated with any human disease.
However, despite its stability, AAV has proved difficult to formulate because it is surprisingly sensitive to a number of different factors, such as the nature of the container, the constituents of the formulation, the temperature of the formulation, as well as changes in temperature, and the concentration of the AAV particles (virions) stored.
AAV vectors are capable of high-frequency stable DNA integration and expression in a variety of cells, including cystic fibrosis (CF) bronchial and nasal epithelial cells human bone marrow-derived erythroleukemia cells and several others.
Unlike retroviruses, AAV does not appear to require ongoing cell division for stable integration; a clear advantage for gene therapy in tissue such as the human airway epithelium where most cells is terminally differentiated and non-dividing.