MicroRNAs Used To Create Safer Cancer Treatments

Viruses--long seen solely as disease agents--now are being used in therapies for cancer. Concerns over the safety of these so-called oncolytic viruses stem from their potential to damage healthy tissues. Now, researchers have discovered a means of controlling the viruses behind potential cancer therapeutics. They are 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 out of control.

"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,” said Stephen Russell, M.D., Ph.D., Mayo Clinic (Rochester, MN, USA) physician-scientist, and lead author of the study.

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

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

The Mayo researchers reported that 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.

The discovery was reported in the October 2008 issue of the journal Nature Medicine.

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