Johns Hopkins University
Barry J. Byrne, M.D., Ph.D.
Paul D. Kessler, M.D.

The following is a summary of the publication in the November 1996 issue of Proceeding of the National Academy of Science, titled “Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein.”

Johns Hopkins University has been investigating the use of a new viral vector, adeno-associated virus (AAV) which has not been previously tested in striated muscle. AAV is a non-pathogenic human parvovirus which has simple single-stranded genome which can be completely replaced with a therapeutic gene.
The result is a vector or vehicle for the delivery of genetic material to cells. It has been found that AAV is able to deliver genes to skeletal muscle and cardiac muscle with high efficiency and that there is sustained expression of the gene in muscle. AAV has been used to express human GAA in human muscle cells in culture and in mice for up to 3 months.
Corresponding studies with erythropoetin have been expressing the therapeutic protein for up to 40 weeks. Therefore, we are encouraged that this approach will be of tremendous utility for inherited disease in general and especially for acid maltase deficiency. We expect that a single intramuscular administration of AAV-GAA may result in long-term expression of GAA which can be secreted into the circulation and taken up by distant tissues. In the near future, we will begin studies to test how much human GAA is made from a repository of muscle tissue in larger animals.
It is encouraging to see how quickly the field of genetic therapies is progressing. But hope must be tempered with the understanding that these experimental therapies are still far from application.
Summary by Barry Byrne, M.D., Ph.D.
(press release follows)