Large Number of Mice Die in Gene Therapy Test
A large number of mice died during a test of RNA interference, a technique used to inactivate genes that cause diseases, according to a study published on Thursday in the journal Nature, the New York Times reports. According to the Times, researchers have begun to use RNAi, in which they insert the proper piece of RNA in cells to inactivate certain genes, in humans to treat diseases, but the study "could give rise to new caution about the technique."
For the study, Dirk Grimm, a postdoctoral researcher at Stanford University, and colleagues used RNAi in the liver cells of mice in an effort to cure them of hepatitis B. Some of the mice were cured without side effects, but others developed liver poisoning, some of which later died.
Among 49 pieces of RNA that researchers inserted to inactivate six different genes, 36 pieces caused liver poisoning, and 23 of those led to death within two months, the study finds. The pieces RNA at the highest concentration were the most toxic, according to the study.
Mark Kay, a researcher involved with the study, said the results are "not a showstopper by any means," adding, "It's like any drug. The toxicity depends on the dose."
Phillip Zamore, an RNAi expert at the University of Massachusetts, said that researchers used a variation of RNAi that was "no longer state of the art" and required a high dosage, adding that the variation of the technique used on humans requires a lower dosage.
John Maraganore -- CEO of Alnylam Pharmaceuticals, which has begun to develop medications through RNAi -- said of the study, "These data really represent the fundamental limitations of gene therapy, not of RNAi."
However, Timothy Nilsen, director of the center for RNA molecular biology at Case Western Reserve University, said, "It's a very striking result -- all of the fatalities observed and the toxicity, which was unexpected. It's really a note of concern for rapid therapeutic development of RNAi" (Pollack, New York Times, 5/25).