Adenovirus-mediated virotherapy is one of the promising therapeutic approaches for
glioma treatment. However, its replication efficiency and specificity still failed to meet the requirements for clinical treatment. To improve the anti-
tumor activity and specificity of oncolytic adenoviruses (OA), we applied multiple
miRNA response elements (MREs) of miR-124, miR-128, miR-146b and miR-218, whose expressions were downregulated in
glioma cells, to enable OA to be specific to
glioma. Adenoviral E1A
protein regulated by these 4 MREs (OA-4MREs) was shown to be highly expressed in
glioma cells, but not in normal cells. The selective E1A expression led to
glioma-specific replication and cytotoxicity of OA-4MREs. Animal experiments also showed that OA-4MREs exhibited improved anti-
tumor activities for both subcutaneous and intracranial
glioma xenografts, without significant toxicity to normal brain and liver tissues. Collectively, we demonstrated that oncolytic adenovirus, whose replication was regulated by MREs, may be promising biological agents for
glioma treatment.