Modified Adenoviruses Better Able to Target and Kill Cancer Cells Due to Addition of AU-Rich Elements That Hasten mRNA Breakdown in Normal Cells, But Which Result in Stabilized mRNA in Cancer Cells, Thus Enhancing Cancer Cell-Specific Killing by the Virus

Hokkaido University scientists have made an adenovirus (graphic image of an adenovirus) that specifically replicates inside and kills cancer cells by employing special RNA-stabilizing elements. The details of the research were published online on May 11, 2020 in the journal Cancers. The open-access article is titled “Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA.” Much research in recent years has investigated genetically modifying adenoviruses to kill cancers, with some of these modified viruses currently being tested in clinical trials. When injected, these adenoviruses replicate inside cancer cells and kill them. Scientists are trying to design more efficient viruses, which are better able to target cancer cells, while leaving normal cells alone. Hokkaido University molecular oncologist Fumihiro Higashino, PhD, led a team of scientists to make two new adenoviruses that specifically target cancer cells. To do this, they used ‘adenylate-uridylate-rich elements’ (AREs or AU-rich elements), which are signals in RNA molecules known to enhance the rapid decay of messenger RNAs (mRNAs) in human cells. “AREs make sure that mRNAs don’t continue to code for proteins unnecessarily in cells,” explains Dr. Higashino. “Genes required for cell growth and proliferation tend to have AREs.” Under certain stress conditions, however, ARE-containing mRNAs can become temporarily stabilized allowing the maintenance of some necessary cell processes. ARE-mRNAs are also stabilized in cancer cells, supporting their continuous proliferation. Dr. Higashino and his team inserted AREs from two human genes into an adenovirus replicating gene, making the new adenoviruses: AdARET and AdAREF.
Login Or Register To Read Full Story