A major drawback to many cancer treatments is that healthy cells can be damaged alongside diseased ones. Approaches that selectively kill only cancerous cells would thus have a distinct advantage over current therapies. Research published in the July issue of the journal Nature Biotechnology may represent progress on that front. Scientists report having engineered a virus that preferentially replicates in tumor cells and subsequently destroys them.
Richard G. Vile of the Mayo Clinic in Rochester, Minn., and his colleagues manufactured an adenovirus that contains a so-called stability sequence, a specific type of messenger RNA (mRNA). The presence of this sequence affects the gene E1A, which is required for viral replication, in different ways depending on the surrounding environment. The researchers hypothesized that in normal cells, the expresssion of E1A should be hindered, inhibiting reproduction of the virus and leaving the cell unharmed. In tumor cells, however, the presence of a protein known as RAS should enhance the stability of the mRNA. With the mRNA protected, so their theory goes, E1A can be expressed, thereby encouraging viral reproduction. When the researchers tested the virus in human tumors both in culture and implanted in mice, they found that it indeed replicated significantly more in tumor cells and successfully slowed tumor growth.
Further refinement of the technique is required because RAS can exist outside of tumors, thus allowing unwanted replication of the virus. But their approach holds promise, the authors note, because there are many different genes that can control the stability of mRNA under conditions associated with various kinds of tumors. A wide variety of viral vectors can therefore be designed for therapy.