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The end of RNAi?
February 8, 2011 8:41 AM   Subscribe

Research on RNA interference is losing steam. Biotech companies are giving the chop to RNAi, a gene-silencing mechanism once thought to have great promise for human medicine.

The Nobel Prize in Physiology or Medicine was given to Fire and Mello for their work on the mechanism in C. elegans. It was originally discovered by Napoli, Lemieux, and Jorgensen in petunias, though they didn’t know what it was. Previously.

Bonus science music videos. You know, for fun.
posted by vortex genie 2 (22 comments total) 8 users marked this as a favorite

 
The end of the article lends some hope for RNAi “A lot of people think it’s winter out there for RNAi,” said John Maraganore, the chief executive of Alnylam. “But I think it’s springtime.”

Also, even if RNAi ends up being a dead end, the pursuit of techniques like this are chock full of worthwhile sub-discoveries. They allow scientists to develop effective strategies. Often times they find it more effective to substitute another technique to further their strategy. But the development of new the new effective strategy might not have happened without RNAi. So yeah, there are no true dead ends when you're developing drugs.
posted by pwally at 9:05 AM on February 8, 2011


Eh. It's just a matter of working on the delivery problem, which is something that academic researchers tend to have a more creative take on than pharma. The academy needs to grind away on this for a few more years, and then you'll start seeing some practical therapeutics.

If nothing else, it's a hell of a research tool for customizing model organisms...
posted by mr_roboto at 9:07 AM on February 8, 2011


Regardless of the lack of miracle cures, RNAi has done amazing things in a short time frame in basic research... hell it even works nicely in non-model organisms. So it's still a boom time as far as I'm concerned.
Also, who exactly is the one "promising" the bounty of drugs from any discovery? This article makes it seem like big Pharma was deceived somehow by nefarious RNAi snakeoil salesmen.
posted by Cold Lurkey at 9:10 AM on February 8, 2011


From the first link: The issue is that while drugs working through the RNAi mechanism can indeed shut off genes, it has been difficult to deliver such drugs to the cells where they are needed. At a time when hard-pressed pharmaceutical companies are already scaling back research expenditures, RNAi is losing out to alternatives that seem closer to producing marketable drugs.

Quoted for those who think we can leave basic science to for-profit enterprises.
posted by Mental Wimp at 9:11 AM on February 8, 2011 [10 favorites]


“A lot of people think it’s winter out there for RNAi,” said John Maraganore, the chief executive of Alnylam. “But I think it’s springtime.”

You know who else it's springtime for?
posted by Faint of Butt at 9:16 AM on February 8, 2011 [8 favorites]


What Cold Lurkey said - I don't give a flip if it works as a medication. It's a great research tool and it will allow medical advances to be discovered.
posted by maryr at 9:34 AM on February 8, 2011


You know who else it's springtime for?

I heard his RNA only has one nucleobase.
posted by Civil_Disobedient at 9:48 AM on February 8, 2011 [1 favorite]


I agree that this will be, at worst, a delay in seeing RNAi getting to the clinic. The big drug companies are scaling back their more speculative research thanks to the economy, but academic labs are still steaming along. If anything, chunks of academia will benefit from this; I know of several labs (mine included) who've decided to go ahead with interesting projects because we know that we're not racing against huge companies. That probably means less data generated in the short term, but more of that data will actually get published and eventual technologies/therapies are likely to be less patent-encumbered than if the drug companies were developing them. So it's a loss, but there are compensations.

Bonus science music videos

I see your science music videos and raise you: Makin' ATP, to the tune of "Make it rain". Genuinely awesome.

Also, Regulatin' genes: less good musically, but I have a soft spot for the hox genes.

I'd also link to the LHC rap, but physicists suck. Thhppbpbpbpt.
posted by metaBugs at 9:52 AM on February 8, 2011 [2 favorites]


"At a time when hard-pressed pharmaceutical companies are already scaling back research expenditures..."

This. Drug companies are currently slashing research efforts across the board. Everything without a high ROI is getting cut, and that includes anything with even a moderate amount of risk. In other words, this says less about the feasibility of iRNA than it does about the current state of the pharmaceutical industry in general.
posted by dephlogisticated at 9:54 AM on February 8, 2011 [1 favorite]


That's funny. Literally the very last thing I did before coming to Metafilter today was shoot an email to the nice folks at Sigma asking for info on a lentiviral shRNA delivery system. Big Pharma may think there's no point in RNAi, and yes, it's likely true that as a drug in and of itself the technique isn't going to work so well. But that's also true for any injectable drug. Best estimates for diffusion of a drug in brain from a point injection range from nowhere to a few millimeters at best. To hit the entire brain area you need to affect for many interventions would require many, many, many injections spread throughout the target region. In humans. In a rat, or a mouse, where the vast bulk of early exploration of concepts is performed, you can usually do it with one well-placed injection. It just doesn't scale well. But that in no way means that RNAi is going away - as a tool for basic science research, it's going to remain as useful as ever. Translational research is what the drug companies are all about - moving from research to product. But a hell of a lot of product has been produced based on concepts that were worked out in model systems. If we know how a mechanism works in a rat or mouse, we can think about how to make changes in people too - just not in the same way.

Saying RNAi is dead is like saying there's no point to knockout mice, just because we can't also create a knockout human (aside from my awesome wife - I know you are all jealous).
posted by caution live frogs at 10:06 AM on February 8, 2011 [2 favorites]


Research on RNA interference is losing steam.

As others have pointed out, in a categorical sense, this is absolutely false. I see RNAi used more and more every year.
posted by grouse at 10:37 AM on February 8, 2011


Monoclonal antibodies were first tried as therapies around 1980. The first FDA approval of a monoclonal antibody was in 1986, really hitting its stride in the late 90s and early 2000s, almost 20 years later. RNAi really only emerged from obscurity around 1998. Give it another ten years before taking its pulse and pronouncing it dead as a therapeutic.

This is the same sort of breathless reporting that pronounced the human genome project a massive failure since it didn't result in a rain of pills from the sky 3 years later. Yet, genome databases have become an integral part of research. They have resulted in new targets, better toxicity testing, and improved side effect profiling. The targets found through genomics are still wending their way through the development process, and will be for another 5-10 years.
posted by benzenedream at 10:49 AM on February 8, 2011 [1 favorite]


Saying RNAi is dead is like saying there's no point to knockout mice, just because we can't also create a knockout human (aside from my awesome wife - I know you are all jealous).

I had to read that three times before I got it. First, I was concerned that you wife had lost her favorite genes. Then I thought she was some sort of mad scientist who experimented on babies. Then I got the joke.
posted by maryr at 11:35 AM on February 8, 2011 [1 favorite]


I had to read that three times before I got it. First, I was concerned that you wife had lost her favorite genes. Then I thought she was some sort of mad scientist who experimented on babies. Then I got the joke.

One thousand one, one thousand two, one thousand three...
posted by Mental Wimp at 11:45 AM on February 8, 2011


This is something I'm really interested in but unfortunately still learning the basics of, however I can't resist reading texts that are above my level (possibly to torture myself?lol)

So here's something I'm wondering about RNA splicing and other gene interventions--- We are looking at peoples genes who "have diseases" seeing the corrolation and assuming that the gene is broken. However what if something was happening in that persons system that the gene was actually adapting to address.

An example would be the recent study that indicated people with allergies are protected from glioma.

What if we're observing these correlations but we're missing the bigger picture and we're really interfering with the bodies coping mechanisms? I love all the research and in saying this, I am not saying we shouldn't do the research because we should. I'm just saying--- what if we're looking up the wrong tree? If we know that toxins and stressors that affect the HPA are affecting epigenetics and also causing damage to the genes-- then perhaps we could also do research on environmental factors that would offer healing effects to genes. (And of course some of this is being done)

It just drives me crazy that at the end of every research article I read I see, "And this offers new insights to gene therapy". It does? It doesn't offer new insights into other therapies as well? Yeesh.
posted by xarnop at 12:22 PM on February 8, 2011


Aah, youth. The privilege and curse of not having long memories. For those who've been around for awhile, this is all a big yawn. Regular like clockwork, every few years there's a new technique, avenue, approach, discover that promises to "revolutionize" medicine. And just as regularly the said revolution dies and with it the hopes of millions of readers of pop science magazines. Science marches on, dead ends are closed off, and sometimes the formerly dead ends, after lying fallow for a long time, lead to new paths.

I remember back in the 80's the whole biotech bubble. We were about to create miraculous drugs left and right as if from computerized programs, where you punch in the disease, and moments later out pops a drug to cure it. Hundreds and hundreds of bio startups soaked up billions upon billions of dollars. And then nothing happened. Yes, we had a couple of successful companies like Genentech, and a few drugs, but that only underlined the paucity of the results after the unbelievable tidal wave of hope and investment.

For those who go back even further, there was the original DNA craze back in the 60's.

Really, science does march on, but real tangible results for medicine - not so much. Cancer is still around as deadly as ever - a lot of the supposed progress is down to games with statistics and interpretations (survival times lengthening transpired to be largely down to earlier diagnosis etc., not actual longer survival times due to therapy).

These days, an oldster with memories greets the newest "discovery" - whatever it may be, say, resveratrol, or "personal drug design", or "X", and yawns. We've seen it all before, and the only thing you can be sure of, is the newest revolution will die a quiet death in inverse proportion to the volume of hype generated at it's inception. The only thing surprising is when someone wakes up and says "remember RNAi? Well, it's not a philosopher's stone after all" - usually there are no obituaries, it's just obscurity. In that way, RNAi is unusual - it actually got an obituary. Of course, there's the school of thought that all results are valuable in science, including the failures, because it all adds to the store of knowledge. Meanwhile, real people will continue to die of various diseases while listening to the siren call of "it's just around the corner", unless they're upbraided for expecting too much of science which is not given to sprints, but rather crawls at a glacial pace - at which point they just die with not even a whisper of hope. True breakthroughs are extremely, extremely rare - it can be counted on the fingers of one hand (things like penicillin/antibiotics, a gaggle of vaccines, and a few others). Yes, yes, we know, RNAi will continue to be fruitful and will add to the store of knowledge, blah, blah, blah, and after visiting, over the weekend, a friend who is dying of brain cancer, I piss on RNAi and the rest of "miracle medicine" from a considerable height.
posted by VikingSword at 12:47 PM on February 8, 2011


Yes, yes, we know, RNAi will continue to be fruitful and will add to the store of knowledge, blah, blah, blah, and after visiting, over the weekend, a friend who is dying of brain cancer, I piss on RNAi and the rest of "miracle medicine" from a considerable height.

VikingSword, I'm sorry your friend is dying. I've been through that before, and am going through it again (Parkinson's and lung cancer, respectively), so I know the feelings of frustration and anger. On the other hand, when my elder daughter was diagnosed with a Wilm's tumor in 1983, I found that over the previous decade, the National Wilm's Tumor Trial had reduced 5-year mortality from 80% to 20% using a combination of vincristine, D-actinomycin, and adriamycin. I enrolled her in that study and today she is a hale and hearty married woman with an MPH and great job with the American Cancer Society. Science does win occasionally, and it should be encouraged on its broken, crooked trail, because it's the only hope we got.
posted by Mental Wimp at 1:10 PM on February 8, 2011 [4 favorites]


It just drives me crazy that at the end of every research article I read I see, "And this offers new insights to gene therapy". It does? It doesn't offer new insights into other therapies as well? Yeesh.

Gene therapy gets special mention because it's awesome, and because the people who work on it are universally erudite, charismatic and fantastic in bed.

Also, because "genes" in the late 90's early 00's is like "radiation" was back in the day. Most people don't really understand what they are, but they sound important and are definitely SCIENCE!y, so they're exciting to talk about. Which is why Spiderman, X-Men, the BBC's (excellent) Day of The Triffids reboot, various zombie films, etc. are all caused by genetic manipulation gone wrong, while a few decades ago they were all caused by weird radiation.
posted by metaBugs at 2:36 PM on February 8, 2011


Uh, Spiderman was totally bitten by a radioactive spider. And X-Men were born that way - they're the next evolution of humankind. Duh.

</dork>
posted by maryr at 2:42 PM on February 8, 2011


I'll concede the X-Men, but in the Spiderman reboot he definitely got his powers from being bitten by a genetically engineered spider.

/ohFSMI'marguingaboutcomicsontheinternetkillmenow
posted by metaBugs at 2:55 PM on February 8, 2011


But that's also true for any injectable drug. Best estimates for diffusion of a drug in brain from a point injection range from nowhere to a few millimeters at best.

Is this really true?
posted by Civil_Disobedient at 3:37 PM on February 8, 2011


Really, hot in bed? I'll have to find me a gene scientist. I hope they like arguing about the nature of genetic evolution in bed because I will so not give that shit a rest lol

I really truly think we are going to uncover that there is so much more to the process that we will due a lot more harm than good with gene therapy at least at this point.

Also I think genes are more succesful than we give them credit. We don't understand them as well as they understand them.

We'd do better to research what stimulates cells to healing their own genetic material and I'm pretty sure I've read a number of studies talking about this.

It seems like cells do a lot of work repairing DNA--- I'm not sure why we aren't identifying which parts of the cell are struggling when something isn't working right, rather than just injecting gene viruses into them.
posted by xarnop at 6:26 PM on February 8, 2011


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