"It may be possible to design and construct genetically engineered 'designer' gene therapy for selectively delivering genes to any part of the body," said Andrew H. Baker, Ph.D., lead investigator of the study and a reader in molecular medicine at the University of Glasgow in Scotland. "We can't do that now because much of what's injected would be sequestered by the liver." The liver cleanses the blood of foreign material, among other functions.
Gene therapy involves inserting the treatment genes into a virus that is either harmless to humans or has had its disease-causing component removed. The virus is then injected or inserted into the body where it "infects" an area with gene therapy.
Baker's team redesigned a virus called adeno-associated virus (AAV) so that it is not quarantined by the liver, but rather remained in the bloodstream long enough to "infect" specific cells in the body -- in this case, the vascular endothelial cells (ECs). The new therapy targets vascular endothelial cells, which line the inside of blood vessels.
"Vascular endothelial cells, which are in continuous contact with the bloodstream and integrally involved in cardiovascular abnormalities, are appropriate targets for gene therapy," Baker said.
Baker said that AAV is important because it has the potential for long-term gene expression from a single dose. This is based on results from hemophilia studies from other laboratories in which the virus was used to deliver gene therapy. In these studies, Baker said that a single dose could last up to five years, possibly longer as the studies are ongoing. AAV is also a good choice because it does not cause disease in humans.