For the last decade, gene therapists have looked for ways to use RNA -- the go-between molecules that help translate DNA code into proteins -- to shut down disease-related genes.
Their hopes were dampened last year, when Stanford University researchers showed that one commonly-used method of so-called RNA interference was lethalc to mice. But according a study published in Nature, MIT scientists may have figured out a way around the toxicity.
The study's press release is nearly unintelligible, which may explain why Reuters was the only outlet to pick the story up. In short, the commonly-used method that went so wrong at Stanford was a highly complicated gene therapy: researchers used a retrovirus to insert a gene into target cells. The gene coded for a type of RNA called short hairpin. The short hairpin RNA then helped produce another type of RNA, called small interfering. The small interfering RNA was responsible for turning off disease genes.
If this sounds a bit Rube Goldbergian, that's because it is. So the ball drops, and it hits the lever, which releases the string that drops the weight that presses the button that.... With so many steps to tweak a cellular system whose mechanisms are still only dimly understood, it's not surprising that something went wrong: specifically, the gene that produced the short hairpin RNA kept making it ... and making it
... and making it.
All this short hairpin ended up messing with the mice's microRNA -- yes, yet another type of molecule. It's responsible for blocking RNA.
And when this part of the system got screwed up, the whole thing failed. The Stanford mice died.
In the latest study, the researchers -- among them biotech titan Bob
Langer -- decided to simplify. Rather using a virus to carry a gene that made an RNA that made another RNA that turned off another gene, they skipped directly to the next-to-last step: adding the small interfering RNA to cellular fluid. It tweaked target genes in their mice, but without messing up their microRNA and killing them.
All the usual caveats apply: it was only one study, just because it's safe in mice doesn't mean it's safe in people, and so on. But at least
RNA interference has hope again.
Study lifts cloud over promising genetic therapy [Reuters]
Effective RNAi-mediated gene silencing without interruption of the endogenous microRNA pathway [Nature]
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