A Method of human Therapy Using Wildtype Adeno-Associated Viral (AAV) Vectors

Applications: human gene therapy

The present invention provides a method of human gene therapy using AAV vectors with essentially wildtype phenotype. Genes of 900 bases or less can be inserted into wildtype AAV and still allow the resulting vector to have a largely wildtype phenotype. For example, several antisense genes could be inserted and still allow packaging. Such wildtype vectors have several advantages. First, high titers of such vectors are easy to accomplish. Second, the vectors, since they include the Rep78 gene, integrate specifically into human chromosome 19. Third, such vectors, being wildtype, spread after their initial introduction. Another method for use of large wildtype AAV genomes is as complementors for fully defective AAV vectors. Such complementors can be delivered by virus infection and, be introduced easily into 100% of the cells used to produce virus. Viral infection is superior to synthetic techniques for introducing DNA into tissue culture producer cells. When large essentially wildtype AAV complementor virus are used in conjunction with AAV vector virus allowing for the introduction of both vectors into all cells, high titers of recombinant AAV virus is achieved.

U.S. Patent #6,153,436

Available for Exclusive Licensing

96-11 Hermonat

Claims:

1. A method of delivering DNA to a target cell, in vitro, using adeno-associated viral vectors, comprising the step of:

administering an adeno-associated viral vector to said cell, wherein said viral vector retain all adeno-associated viral genomic sequences, wherein said viral vector contains a DNA insert of a size up to about 1000 nucleotide base pairs and wherein said insert is placed after the last coding region of said virus and prior to the right ITR of said virus.

2. The method of claim 1, wherein said DNA insert is less than 900 nucleotide base pairs

3. The method of claim 1, wherein said DNA insert is inserted into a non-essential portion of the viral vector, wherein non-essential portions do not harbor cist or trans sequences that are required for viral replication or transcription.

4. The method of claim 1, wherein said viral vector integrates into chromosome 19 of said cell.

5. A method of complementing a defective adeno-associated viral vector, comprising the step of:

administering a defective adeno-associated viral vector to a cell, in vitro; and
administering a non-defective adeno-associated viral vector to said cell, said non-defective viral vector retaining all adeno-associated viral genomic sequences, wherein said non-defective viral vector contains a DNA insert of a size up to about 1000 nucleotide base pairs and wherein said non-defective viral vector is capable of generating virus particles of the defective adeno-associated viral vector.

No known limitations

File Number: 96-11 

Web site: http://www.uams.edu/bioventures

Disease: Infectious Diseases

Other Information:

Available for Exclusive Licensing