Nuria Morral

School of Medicine, Medical & Molecular Genetics

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Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons

Núria Morral; Wanda K. O'Neal; Karen Rice; M. Michelle Leland; Pedro A. Piedra; Estuardo Aguilar-Córdova; K. Dee Carey; Arthur L. Beaudet; Claire Langston (Profiled Author: Nuria Morral)

Human Gene Therapy. 2002;13(1):143-154.

The effects of intravenous administration of a first-generation adenoviral vector expressing β-galactosidase were compared in two baboons receiving a high dose or lower dose of vector, 1.2 × 10 ¹³ or 1.2 × 10 ¹² particles/kg, respectively. The high-dose baboon developed acute symptoms, decreased platelet counts, and increased liver enzymes, and became moribund at 48 hr after injection, while the lower-dose baboon developed no symptoms. Expression of the β-galactosidase transgene was prominent in liver, spleen, and endothelium of the arterial vasculature in the high-dose baboon, but was much more limited and spared the endothelium in the lower-dose baboon. Injury to the vascular endothelium was the most prominent abnormality in the high-dose baboon. Extensive histological studies provide a detailed picture of the pathology associated with a lethal dose of first-generation adenoviral vector in a primate.

PMID: 11779418    

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