RNA interference proves fatal
The hope that so-called RNA interference will soon be used to combat various diseases must be clearly dampened. Researchers at Stanford University report a failed experiment in which they attempted to introduce various shRNAs (short-hairpin RNAs) with a virus into rat liver cells and then allowed them to be expressed over a longer period of time. After some time, however, the animals reacted to almost three quarters of the foreign RNA variants tested with liver disease, and almost half even killed the test rodents in the end.
In RNA interference, so-called shRNAs are used to switch off specific genes in a cell. Apparently, the short RNA molecules in the Stanford researchers' experiments got in the way of other cell processes in the long term. The scientists suspect that the artificial, long-term production of the introduced shRNAs competes with the production of the cell's own, vital microRNAs. Apparently, there is an upper limit to the capacity of the cell machinery in the production of short RNA molecules, according to study leader Mark Kay.
Nevertheless, the researchers also achieved success: an shRNA introduced into mouse livers, but only expressed in small amounts there, was able to specifically slow down hepatitis C viruses without side effects.
Overall, however, the researchers are calling for the previously considered strategy to be reconsidered, according to which simply larger amounts of specific shRNA should be introduced into cells for therapy to block unwanted genes. Instead, the amount of shRNA in cells probably needs to be tightly regulated.
