Micromanaging oncolytic viruses
Oncolytic viruses have had limited success as cancer therapies, largely because of the need to balance potent antitumor activity with off-target toxicity. Two research teams have now applied a microRNA-based strategy that could restrict the replication of oncolytic viruses to tumors without the need for alterations to the viral genome that can lead to an overly attenuated strain.1,2
Oncolytic viruses are engineered to selectively target and replicate within tumor cells, triggering lysis and cell death. Selective targeting is usually achieved by mutating the viral genome to lower the likelihood that the virus will target or replicate within healthy cells. However, these mutations carry the risk of weakening the virus strain's ability to replicate within the tumor. Thus, attempts to balance potency and off-target pathogenicity have led to oncolytic viruses that are safe but lack efficacy in the clinic (see Table 1, "Oncolytic virus therapies").3,4
Enter miRNAs, which are single-stranded, noncoding RNA molecules that downregulate gene expression by targeting specific mRNAs and preventing protein translation.
The key is that miRNA expression patterns are often tissue-specific. Thus, the two groups of researchers