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June 5, 2020 /
BiovalleyBIOON / -- Adenoviruses are now better able to target and kill cancer cells thanks to the addition of RNA stabilization factorsscientists at Hokkaido University inhave created an adenovirus that replicates inside cancer cells and kills cancer cells with special RNA stabilization factorsDetails of the study were published in the journal Cancerin recent years, many studies have been looking at genetically modified adenoviruses to kill cancer, some of which are currently beingclinical trialsWhen injected intotumortissue, these adenoviruses replicate and kill them in cancer cellsScientists are trying to design a more efficient virus that better attacks cancer cells without harming normal cellsimage source: CancerFumihiro Higashino, a molecularoncologist at Hokkaido University, led a team of scientists to create two new adenoviruses targeting cancer cellsTo do this, they used "arinter-rich elements" (AREs), a signal in RNA molecules that are known to accelerate the rapid decay of messenger RNA (mRNAs) in human cells"AREs ensure that mRNAs do not continue to encode unnecessary proteins in cells," Higashino explains"The genes needed for cell growth and proliferation often contain AREs"
However, under certain stress conditions, mRNAs containing ARE can be temporarily stabilized to maintain some necessary cellular processesARE-mRNAs are also stable in cancer cells, supporting their continued proliferationHigashino and his team inserted AREs from two human genes into one adenovirus replication gene to create new adenoviruses: AdARET and AdAREF"Our idea is that AREs will stabilize anti-adenoviruses so that they can only replicate within cancer cells, not in normal healthy cells," Higashino said"
in fact, both AdARET and AdAREF were found to replicate and kill cancer cells in the lab with little effect on normal cellsTests have shown that specific replication of cancer cells is due to the stability of viral genes and AREs, which are not found in healthy cellsthen, the scientists injected human cancer cells into the skin of naked mice, which then developed into tumorsWhen AdARET and AdAREF are injected into the tumor, they cause a significant reduction in the size of thetumorthis is not the first time the team has tested AREs for applications in adenovirusesIn a previous study, another scientist used ARE, another gene, to find that the adenovirus is particularly effective in cancers that contain mutations in the RAS geneOn the other hand, AdARET and AdAREF were found to be effective against cancer cells without a mutation in the RAS gene, which makes these viruses suitable for a wider range of cancer cells "Because other diseases besides cancer have been reported to indicate the stability of ARE-mRNA, we believe that the virus we designed may also be used to treat diseases related to inflammation, viral infections, hypoxia and UV exposure," said Higashino, a (biovalleybioon.com) reference: Exploiting viruses to attack cancer cells
Yohei Mikawa et al.
Conditionly Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA, Cancers (2020) DOI: 10.3390/cancer12051205