Gene Silencing

Breakthrough technology with RNA on neurons.


DNA is deoxyribonucleic acid, or the building blocks of the chromosomes. This was discovered by Jim Watson and Francis Crick (Dr. Crick, recently deceased, is one of the authors at painonline).

The chromosome codes for mirror sequences of nucleotides to produce RNA or ribonucleic acid. Adenine and Thymine in DNA are substituted as Uracil and Guanine in RNA. The RNA moves to the cytoplasm where ribosomes read the code transferred to attract amino acids in the sequence necessary to produce peptides, which are chains of amino acids less than 200 units in length. Longer than this are called proteins, which are still amino acids, but have very complicated shape and configuration due to bonding angles of the atoms and configurational torsions of the molecules.

In this month’s Nature, 2007, Kumar et al report development of a technique to silence genes.

As you know, rabies can infect the central nervous system, ie. it can pass the blood/brain barrier which is a common problem in trying to get enough of any drug to the central nervous system. Kumar therefore extracted a short peptide from Rabies virus glycoprotein (RVG). The peptide binds to the acetylcholine receptor found in neurons. Attaching this peptide to a small intefering RNA (siRNA) allowed specific silencing of genes. It was possible to prevent viral meningitis after deliberate infection in rats using this technique.

Very significantly, by using only small RNA, no inflammatory cytokines were induced and NO antibodies against the peptide occurred.

This is clearly a brave new world. Small intefering RNA should be able to silence not only the genes required for proliferation of viruses causing meningitis, but theoretically any gene at all. Tomorrow’s medicines against pain may be almost entirely small interfering RNA which prevents activity in the TRPV-1 channel, specifically in the loop between domains 5 and 6 to which all the potent pain chemicals attach.

siRNA is basically a silver bullet against any gene which complements(matches) it.

Kumar is at Harvard, the CBR Institute.

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For more on gene silencing, see http://www.ambion.com/techlib/hottopics/rnai/