Your Next Cancer Therapy May Be A Virus
    By News Staff | October 26th 2008 06:15 PM | 1 comment | Print | E-mail | Track Comments
    Viruses aren't just disease agents any more.  Scientists now know they can be used in therapies for cancer but concerns over the safety of  'oncolytic viruses' remain because they can also damage healthy tissues.

    But Mayo Clinic researchers say they have discovered a way of controlling the viruses behind potential cancer therapeutics by engineering the virus's genetic sequence, using microRNAs to restrict them to specific tissues. The microRNAs destabilize the virus's genome, making it impossible for the virus to run amok. The discovery is reported in the current issue of Nature Medicine.

    MicroRNAs are the nucleotide snippets that are encoded by genes, but don't end up as proteins. In many cases, they have a role in down-regulating different cellular genes. In this case, a virus is engineered to be responsive to microRNAs that are present in certain cell types. Using this new form of targeting, researchers redirected a virus normally responsible for a lethal muscle infection to recognize only cancer cells. The laboratory mice that received the engineered virus were cured of established tumors and suffered no ill effects.

    "Our findings demonstrate a new tool for molecular medicine that should also help allay concern over the use of viruses as a therapeutic delivery system," says Stephen Russell, M.D., Ph.D., Mayo physician-scientist and lead author of the study.

    Significance of the research

    Most viruses can infect different cell types, which leads to the array of symptoms during a viral infection. Now as viruses are being engineered for use as vaccines, cancer therapeutics and gene therapy vectors, researchers want to restrict and redirect the types of cells they do (or don't) infect as additional safeguards against disease. The target sequences of microRNAs used in the study kept the virus from destroying muscle cells while allowing viral replication to proceed in cancer cells allowing the virus to completely cure mice with melanoma.

    The Mayo researchers say microRNA target insertion may be a new way to make viruses safer for use in cancer therapy and could lead to new methods of making safer vaccines.


    MicroRNA target insertion has been recently used in an oncolytic herpes simplex virus design to specifically destroy prostate tumors, while leaving normal tissues intact. In a relatively recent article published by W. Jia and his colleagues (Lee et al., 2009), they used a microRNA target sequence to regulate the expression of an essential viral gene ICP27 that is absolutely required for virus replication. They were able to show that by insertion of microRNA target sequence (for microRNA-143 that is downregulated exclusively in cancer cells) at the 3' untranslated region of ICP27 gene, the virus destroyed only cancer cells through oncolysis. In vivo studies show that the virus is remarkably effective in destroying tumors, and is minimally toxic when injected intravenously.  It looks like the virus may be on its way to becoming the next anti-cancer therapeutic.

    For more information, read-
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    <![endif]-->Lee, C., P.S. Rennie, and W. Jia, MicroRNA Regulation of Oncolytic Herpes
    Simplex Virus Type 1 for Selective Killing of Prostate Cancer Cells.
    Cancer Res, 2009