Exposure to AAV either as an intact virus or as a recombinant vector shell affected gene expression minimally and in patterns not associated with potential harm to the host organism, the report said. In addition, exposure to the empty capsid of AAV - the protein coat of the virus devoid of DNA - also produced minimal response from the genes. For example, only 1.9 percent of genes showed changes in expression in cells infected by recombinant AAV.
In contrast, gene expression after exposure to intact adenovirus and recombinant adenovirus vector was much broader and included the activation of immune and stress response genes. Lung cells exposed to empty adenovirus capsid showed a decrease in changes in cellular gene expression, although some were related to stress response genes.
This study provides a systematic explanation for the relative safety profiles of two commonly used gene therapy vector classes, Samulski said.
"The take-home message here is we can now monitor the genes that get turned on when you put a vector on the cell," he said. "We can then make changes to the vectors and observe how their safety profiles improve prior to their use clinically."
"As we make architectural changes to the delivery system, we can see the cell's response to it," Stilwell added. "The study represents the start of a useful database of gene expression signatures for people involved in vector development."
The next step for the UNC researchers is to continue exploring the vector-associated gene expression signatures in other cell types and to extend the work to whole animals.
"I think everybody involved in designing vectors will continue to build o
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Contact: Leslie H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
23-Feb-2004