Biodistribution of an oncolytic adenovirus after intracranial injection in permissive animals: A comparative study of Syrian hamsters and cotton rats

A. M. Sonabend, I. V. Ulasov, Y. Han, C. E. Rolle, S. Nandi, D. Cao, M. A. Tyler, M. S. Lesniak

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Conditionally replicative adenoviruses (CRAds) are often evaluated in mice; however, normal and cancerous mouse tissues are poorly permissive for human CRAds. As the cotton rat (CR) is a semipermissive animal and the Syrian hamster (SH) is a fully permissive model for adenoviral replication, we compared them in a single study following intracranial (i.c.) injection of a novel glioma-targeting CRAd. Viral genomic copies were quantified by real-time PCR in brain, blood, liver and lung. The studies were corroborated by immunohistochemical, serological and immunological assays. CR had a multiple log higher susceptibility for adenoviral infection than SH. A similar amount of genomic copies of CRAd-Survivin-pk7 and human adenovirus serotype 5 (AdWT) was found in the brain of CR and in all organs from SH. In blood and lung of CR, AdWT had more genomic copies than CRAd-Survivin-pk7 in some of the time points studied. Viral antigens were confirmed in brain slices, an elevation of serum transaminases was observed in both models, and an increase in anti-adenoviral antibodies was detected in SH sera. In conclusion, CR represents a sensitive model for studying biodistribution of CRAds after i.c. delivery, allowing for the detection of differences in the replication of CRAd-Survivin-pk7 and AdWT that were not evident in SH.

Original languageEnglish (US)
Pages (from-to)362-372
Number of pages11
JournalCancer Gene Therapy
Volume16
Issue number4
DOIs
StatePublished - Apr 2009

Keywords

  • Biodistribution
  • Cotton rat
  • Glioma
  • Oncolytic adenovirus
  • Replication
  • Syrian hamster

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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