Enhancing gene therapy

Successful gene therapy treatment for cancer requires effective targeting of viruses that replicate only in tumor cells, but selective gene expression with adenoviral vectors has been difficult to achieve. Expression of various tumor-associated proteins is significantly enhanced in many tumors, partly by stabilization of their mRNAs through adenosine-uridine rich sequences in the 3′ untranslated regions (UTRs). In the June 8 advanced online publication Nature Biotechnology, Atique Ahmed and colleagues at the Mayo Clinic show that tumor cell selective stabilization of mRNA can be used to control therapeutic gene expression in cancer gene therapy viral vectors (Nature Biotechnology, DOI:10.1038/nbt835, June 8, 2003).

Ahmed et al. created a conditionally replication competent adenoviral vector in which expression of the essential E1A gene is regulated by ligation to the 3′UTR of PTGS2 (also known as COX2), allowing activated RAS/P-MAPK–specific stabilization of its mRNA. They observed that the Ad-E1A-COX virus is preferentially oncolytic in vitro ...