Transcytosis of Adeno-Associated Viruses

The invention relates to a method for delivering nucleic acids to a variety of cells including those of the gut, kidney, lung and central nervous system. The underlying cells of such organs are covered by a barrier of endothelial or epithelial cells which can limit the transfer of nucleic acids, or other potentially therapeutic agents, to the underlying target cells. To overcome this limitation, the method employs certain members of the parvovirus family to transcytose the barrier cells. During transcytosis, the virus passes through these barrier cells and can infect cells of the underlying layer. Therefore, this method could facilitate the transfer of nucleic acids to cells that currently available viral vectors are unable to reach.

The method could be applied to the treatment of neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Huntington’s, lysosomal storage diseases, the dominant spinal cerebellar ataxias, and Krabbe's disease without the need for stereotactic injection. The method could potentially also be used in the treatment of genetic muscle disorders such as muscular dystrophy. Several of the viruses described in the invention are serologically distinct and could be used in patients who have developed an immune response to other vectors. This work is part of an ongoing effort to development AAV vectors for gene transfer. Other key technology related to this invention, such as several vector platforms, production, purification methods, and target cell tropism is available for licensing.