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

Nuria Morral, Wanda K. O'Neal, Karen Rice, M. Michelle Leland, Pedro A. Piedra, Estuardo Aguilar-Córdova, K. Dee Carey, Arthur L. Beaudet, Claire Langston

Research output: Contribution to journalArticle

151 Citations (Scopus)

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 × 1013 or 1.2 × 1012 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.

Original languageEnglish (US)
Pages (from-to)143-154
Number of pages12
JournalHuman Gene Therapy
Volume13
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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Papio
Wounds and Injuries
Galactosidases
Endothelium
Liver
Vascular Endothelium
Platelet Count
Transgenes
Intravenous Administration
Primates
Spleen
Pathology
Injections
Enzymes

ASJC Scopus subject areas

  • Genetics

Cite this

Morral, N., O'Neal, W. K., Rice, K., Leland, M. M., Piedra, P. A., Aguilar-Córdova, E., ... 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

Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. / Morral, Nuria; O'Neal, Wanda K.; Rice, Karen; Leland, M. Michelle; Piedra, Pedro A.; Aguilar-Córdova, Estuardo; Carey, K. Dee; Beaudet, Arthur L.; Langston, Claire.

In: Human Gene Therapy, Vol. 13, No. 1, 2002, p. 143-154.

Research output: Contribution to journalArticle

Morral, N, O'Neal, WK, Rice, K, Leland, MM, Piedra, PA, Aguilar-Córdova, E, Carey, KD, Beaudet, AL & Langston, C 2002, 'Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons', Human Gene Therapy, vol. 13, no. 1, pp. 143-154. https://doi.org/10.1089/10430340152712692
Morral, Nuria ; O'Neal, Wanda K. ; Rice, Karen ; Leland, M. Michelle ; Piedra, Pedro A. ; Aguilar-Córdova, Estuardo ; Carey, K. Dee ; Beaudet, Arthur L. ; Langston, Claire. / Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. In: Human Gene Therapy. 2002 ; Vol. 13, No. 1. pp. 143-154.
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