Cellular Characterization of the Tropism of Recombinant Adenovirus for the Adrenal Glands

Background: Recombinant adenoviruses are widely used in gene therapy clinical trials. A particular tropism for the adrenal glands has been reported but the precise cellular base for this tropism has not been determined.

Materials And Methods: Recombinant adenoviruses were injected intravenously into Balb/c nu/nu or C57BL/6 mice. Seventy-two hours later, the animals were sacrificed and the adrenal glands and livers collected. The glands were sectioned and analyzed using immunohistochemical methods to detect adenoviral epitopes and transgene expression. Total RNA were extracted from the liver and adrenal glands of some animals and subjected to real-time RT-PCR.

Results: The only cell type infected in the adrenal glands of Balb/c nu/nu or C57BL/6 mice is the adrenocortical cells in the zona fasciculata. Quantitatively, the relative level of gene expression in the adrenal gland is comparable but lower than that measured in the liver.

Conclusions: Systemic injection of recombinant adenovirus could be used as a procedure to restore adrenal steroidogenesis in clinical gene therapy protocols. In addition, our study suggest that adrenal dysfunction should be considered when criteria are established to assess the safety of gene therapy formulations administered systemically.