RNAi – STREAM research

For Whom the Cell Tolls?

A month ago or so, I wrote about a new gene-based strategy against disease: RNAi. Recall that in 2006, Andrew Fire and Craig Mello won Nobel Prizes in Medicine for the discovery of RNAi.

The idea of using RNAi in therapeutic applications would be to administer these small genetic sequences to “knock down” the activity of certain, aberrant genes. Because they function on the basis of genetic complementation, RNAi therapies should be highly specific. Such specificity is key for limiting side effects, which are often caused when drugs stray to the wrong target.

As with almost all novel technologies (and, in particular, genetic ones), researchers will not have an EZ-Pass in attempting to translate RNAi to the clinic. In a recent issue of Nature (and a corresponding news story by Andrew Pollack in the NYTimes on April 2), researchers reported that any sequence consisting of 21 or so nucleotides could trigger a physiological effect (angiogenesis inhibition) in mice through a generic mechanism, the “Toll-like Receptor 3” pathway. The study is particularly troubling, because it suggests that RNAi (or, at least certain types of RNAi) might be prone to worrisome side-effects.

According to Pollack, at least five such drugs are presently being tested in human beings. (photo credit: pbo31, 2005)

2008 April 3 | Leave a comment | Tags: RNAi

BibTeX

@Manual{stream2008-164,
    title = {For Whom the Cell Tolls?},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = apr,
    day = 3,
    url = {http://www.translationalethics.com/2008/04/03/for-whom-the-cell-tolls/}
}

MLA

Jonathan Kimmelman. "For Whom the Cell Tolls?" Web blog post. STREAM research. 03 Apr 2008. Web. 10 Jan 2025. <http://www.translationalethics.com/2008/04/03/for-whom-the-cell-tolls/>

APA

Jonathan Kimmelman. (2008, Apr 03). For Whom the Cell Tolls? [Web log post]. Retrieved from http://www.translationalethics.com/2008/04/03/for-whom-the-cell-tolls/

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siRNA: Caveat Emptor for Preclinical Studies?

by Jonathan Kimmelman

Small interfering RNA molecules (siRNA) are generating a lot of excitement in biomedical research for their ability to “knock down” specific genes– say, those of an invading virus or a tumor cell.

But because viruses tend to produce small pieces of RNA, the body often “interprets” siRNA as a viral infection and launches an immune response. In the Februrary 2008 issue of Human Gene Therapy, Adam Judge and Ian Maclachlan of Protiva Biotherapeutics describe some of the consequences of this. A major one is that studies testing siRNA in animals or humans might be prone to false positives, especially for medical conditions where the immune system is implicated in disease control. The problem is (according to these authors, at least), there seems to be little consensus about how to design experimental controls to sift true from spurious claims of specific efficacy. Yet another complication in the interpretation of preclinical studies, as well as the decision to initiate human testing.

2008 February 27 | Leave a comment | Tags: RNAi

BibTeX

@Manual{stream2008-176,
    title = {siRNA: Caveat Emptor for Preclinical Studies?},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = feb,
    day = 27,
    url = {http://www.translationalethics.com/2008/02/27/sirna-caveat-emptor-for-preclinical-studies/}
}

MLA

Jonathan Kimmelman. "siRNA: Caveat Emptor for Preclinical Studies?" Web blog post. STREAM research. 27 Feb 2008. Web. 10 Jan 2025. <http://www.translationalethics.com/2008/02/27/sirna-caveat-emptor-for-preclinical-studies/>

APA

Jonathan Kimmelman. (2008, Feb 27). siRNA: Caveat Emptor for Preclinical Studies? [Web log post]. Retrieved from http://www.translationalethics.com/2008/02/27/sirna-caveat-emptor-for-preclinical-studies/

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For Whom the Cell Tolls?

siRNA: Caveat Emptor for Preclinical Studies?

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