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-CɃrdova, K. Dee Carey, Arthur L. Beaudet, Claire Langston

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

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 × 1013or 1.2 × 1012particles/kg, respectively. The high-dose baboon developed acute symptoM.S., 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.

Original languageEnglish (US)
Pages (from-to)143-154
Number of pages12
JournalHuman gene therapy
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Morral, N., O’Neal, W. K., Rice, K., Leland, M. M., Piedra, P. A., Aguilar-CɃrdova, E., Carey, K. D., Beaudet, A. L., & Langston, C. (2002). Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. Human gene therapy, 13(1), 143-154. https://doi.org/10.1089/10430340152712692