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.
Bibliographical noteFunding Information:
We are grateful to the animal facility at the University of Chicago for their advice and technical support. In addition, we acknowledge the support of Ms Terri Li from the immunohistochemistry facility at the University of Chicago. This work was supported by the National Cancer Institute (R01-CA122930, MSL), the National Institute of Neurological Disorders and Stroke (K08-NS046430, MSL), The Alliance for Cancer Gene Therapy Young Investigator Award (MSL) and the American Cancer Society (RSG-07-276-01-MGO, MSL).
- Cotton rat
- Oncolytic adenovirus
- Syrian hamster