An adenovirus is now better able to target and kill cancer cells due to the
addition of an RNA stabilizing element
From:
Hokkaido University in Japan
May
28, 2020 -- Hokkaido University scientists have made an adenovirus that
specifically replicates inside and kills cancer cells by employing special
RNA-stabilizing elements. The details of the research were published in the
journal
Cancers.
Much
research in recent years has investigated genetically modifying adenoviruses to
kill cancers, with some 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 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), 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 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.
Higashino
and his team inserted AREs from two human genes into an adenovirus replicating
gene, making the new adenoviruses: AdARET and AdAREF. “The idea behind the
insertion is that the AREs will stabilize the killer adenoviruses, allowing
them to replicate only inside cancer cells but not in normal healthy ones,”
says Higashino.
Indeed,
AdARET and AdAREF were both found to replicate inside and kill cancer cells in
the laboratory, while they hardly affected normal cells. Tests confirmed that
the specific replication in cancer cells was due to stabilization of the viral
genes with AREs, which did not happen in the healthy cells.
The
scientists then injected human cancer cells under the skin of nude mice, which
then developed into tumors. When AdARET and AdAREF were injected into the
tumors, they resulted in a significant reduction in tumor size.
This
wasn’t the first time for the team to test the use of AREs in adenoviruses. In
a previous study, another scientist used an ARE belonging to a different gene
and found this adenovirus worked specifically in cancers containing a mutation
in a gene called RAS. AdARET and AdAREF, on the other hand, were found
to be effective against cancer cells without a mutated RAS gene, making the
viruses applicable to a wider range of cancer cells.
“Since
ARE-mRNA stability has also been reported in diseases other than cancer, we
think the viruses we engineered could also have potential for treating diseases
related to inflammations, viral infection, hypoxia, and ultraviolet
irradiation,” says Higashino.
https://www.global.hokudai.ac.jp/blog/exploiting-viruses-to-attack-cancer-cells/