Neurotoxicity of intracerebral injection of a replication-defective adenoviral vector in a semipermissive species (cotton rat)

H. D. Shine, P. R. Wyde, E. Aguilar-Cordova, S. H. Chen, S. L C Woo, R. G. Grossman, J. C. Goodman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The neurotoxicity of an adenoviral vector (Adv.RSVtk) carrying the gene for herpes simplex virus thymidine kinase (HSVtk) was tested in the cotton rat, a semipermissive host. Adv.RSVtk was injected intracerebrally in cotton rats at a dose of 5.0 x 106 or 7.5 x 107 p.f.u. No signs of illness were observed. Histological inspection at 12 a 28 days after injection showed inflammation of the ependyma and choroid plexus and at the injection site. No demyelination, viral inclusions, cerebral edema, necrosis, cavities or vascular necrosis were seen in the brains. There was no significant difference between animals injection with 5.0 x 106 or 7.5 x 107 p.f.u., nor was there a difference between animals analyzed at 12 or 28 days after vector injection. This inflammation was similar in animals that had been pre-immunized with wild-type virus and in animals that had been treated with ganciclovir. No histopathology was observed in the lungs of the animals and no replication-competent virus was detected. These experiments indicate that Adv.RSVtk had limited neurotoxicity which would not prohibit its use in a limited phase l clinical trial in humans that have malignant tumors of the central nervous system.

Original languageEnglish (US)
Pages (from-to)275-279
Number of pages5
JournalGene Therapy
Volume4
Issue number4
DOIs
StatePublished - Jan 1 1997

Keywords

  • Adenoviral vector
  • Brain
  • Cotton rat
  • Neurotoxicity

ASJC Scopus subject areas

  • Genetics

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