In the study, led by Robert E. Braun, Ph.D. Associate Professor of Genetics at the University of Washington, gene expression after adenovirus delivery was analyzed from a series of both in vitro and in vivo studies. The in vitro studies demonstrated that germ cells grown in cell culture were refractory to infection by Collaterals adenovector. To assess the risk of germ line transmission in vivo, researchers used a mouse model to deliver human recombinant Ad5 carrying a germ cell-specific promoter fused to a reporter gene directly into the left ventricular cavity of the heart. They observed that the reporter gene protein was not expressed in developing spermatids or mature sperm, with analyses performed at multiple time points after administration to evaluate all major stages of germ cell development. Importantly, the in vivo studies did not detect infection of the reproductive stem cells. The positive results from these studies are consistent with other recent studies using different models and routes of delivery. However, this is the first study that directly assessed the ability of an adenovirus to result in gene expression in extremely large numbers (i.e., millions) of germ line cells, and the first to assay infection of the reproductive stem cell population.
This study provides significant new information further supporting the safety of the use of the adenovirus as a vehicle to deliver therapeut
Contact: Lora Pike