Adenoviral vector-mediated gene expression in the nervous system of immunocompetent Wistar and T cell-deficient nude rats: preferential survival of transduced astroglial cells in nude rats

Human Gene Therapy
W T Hermens, J Verhaagen

Abstract

In the present paper, we examined the effect of the adenoviral vector dosage, the role of T cells, and the influence of the presence of replication-competent adenovirus (RCA) in adenoviral vector stocks, on the efficacy of adenoviral vector-directed transgene expression in the facial nucleus of immunocompetent Wistar and athymic nude rats. A small number of motor neurons and glial cells was transduced at low dosages of viral vector (1 x 10(6) pfu) and in the absence of RCA, and transgene-expressing cells persisted throughout the 3-week period of observation. Intraparenchymal infusion of 2 x 10(7) pfu of a recombinant adenoviral vector free of RCA was required for optimal transduction of facial motor neurons. In Wistar rats, a biphasic immune response occurred at higher dosages of the vector (5 x 10(6) and 2 x 10(7) pfu) that was characterized by early infiltration of macrophages and the occurrence of T cells during the second week after injection of the vector. The immune response was associated with the loss of transduced neural cells. In nude rats, administration of an adenoviral vector free of RCA resulted in a macrophage response comparable to that in the Wistar rat and long-term survival of transduced astroglial cells. How...Continue Reading

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