Last evening, I was discussing the concept of gene silencing with a friend of mine out of necessity. To be honest, discussion would not be the word for “discussion” presupposes a certain amount of parity in knowledge and the level of understanding of both the parties on the subject, which by any stretch of imagination wasn’t the case here; so it wouldn’t be off the mark to say that I had requested him to “explain” the concept to me. Incidentally, biology and I have been poles apart. Yet I give it to my friend for so lucidly explaining the basic technology involved.According to him, every gene expresses itself following the central dogma where transcription of DNA to RNA to protein takes place with major intermediary stages being replication of information in DNA using enzymes, followed by coding of DNA for production of messenger RNA (mRNA) during transcription. The mRNA is then processed and finally the coded information of mRNA is translated in ribosomes for protein synthesis. These proteins are involved in almost all biological activities. I then asked him to explain gene silencing in this context to which he first pointed out, in brief, the technologies prior to the development of gene sequencing. In layperson’s terms, according to him, if a particular disease or a disorder was traced to a particular gene, then usually that portion was lobbed off or one had to resort to other forms of gene modification.
Gene silencing apparently is a much more subtle technique where instead of doing away with the gene altogether, the gene is “turned off”, in other words, brakes are applied in the transcription process and the expression of the gene till the point it becomes a protein, is prevented. Then, I did what most people who are frantically in search of information do- google. This (Google) most blest fruit of fertile human imagination and the life-saver that it is, revealed to me that there are transcriptional and post-transcriptional methods of gene silencing. RNAi or Ribose Nucleic Acid interference falls within the latter and incidentally this discovery won the Nobel Prize in medicine in the year 2006. Livemint informs us that global RNAi research now has an Indian connection. According to the Livemint article, Utpal Bhadra, a senior scientist at Centre for Cellular and Molecular Biology (CCMB), Hyderabad, showed in as early as 1997 that gene could be silenced in fruit flies and then decided to extend the application of this technology to help in better diagnosis of cancer. However, the path to this is full of thorns- patents. Dr.Bhadra says:
“It’s very difficult to develop new therapeutics with RNAi as most of the patents are owned by US-based Sirna Therapeutics Inc., and Alnylam Pharmaceuticals Inc.,”
This information saved me the effort of having to scourge patent databases for statistics; yet out of force of habit i ran a random search to be informed that there are about 563 patents on this technology. The article further says:
With at least four major milestones in the basic science of RNAi since 1997 to his credit, Bhadra is now trying to modify the technique to bypass the patents. In close collaboration with a local biotech company, whose name he doesn’t want to disclose, Bhadra is developing an “easy-shot” diagnostic kit which will use microRNA (miRNA) profiling as a molecular marker for predictive diagnosis of cancer. The tiniest entities in the human genome, miRNAs, have been lately found to be involved in regulating almost a third of all human genes. In other words, these tiny single-stranded molecules, estimated to be about 1,000 in number, control the turning on and off of a gene. Complementing it is RNAi, a naturally occurring process in the cell for silencing specific genes.
Bhadra says his diagnostic programme will be a complete, packaged test, ranging “from testing the susceptibility of the disease to its sub-classification and stage detection”. The technology is set to enter clinical trials in three months and “if it’s successful” Bhadra will file for a global patent. Along with his wife and close collaborator at the Indian Institute of Chemical Technology Manika Pal, Bhadra says he is also trying to use this machinery to try prevent HIV, Japanese Encephalitis and cancer. He wants to generate RNAi-based screens for HIV which would also be a sort of library to screen for genes involved in nearly any process of scientific interest.
These are of course long-term goals and Bhadra is already acting as a chief technology officer, of sorts, for a company, iBrain Life Sciences, which intends to develop RNAi-based therapeutics as well as use this technique to “artificially engineer stem cells”.
“We have acquired land for a hospital where our clinical research in cell therapy will be carried out,” said Shravan Rao, chief operating officer of iBrain.
Enormously potent as this technology is, scientists believe laying down basic infrastructure for cell-based therapies is the responsibility of state-funded institutions. “You cannot expect the industry to invest in such areas,” said Lalji Singh, director of CCMB, who is setting up a “high throughput screening” facility for RNAi.
“Just a handful of such facilities exist in the US and we are trying to set it up here so that if one needs to diagnose cancer, the RNAi can be screened against all 25,000 genes (the approximate number of genes in the human genome) to check which one is effective in silencing the defective gene,” said Singh. He thinks only then will RNAi become useful for commercial purposes.
In fact, commercial opportunities of the study extend to agriculture as well. RNAi can be used to make transgenic crops, which are not controversial such as the traditional genetically modified crops because they are made by a natural process inbuilt into cells to combat viruses.
Not to sound priggish, but finally I have good reason, for however brief a time, to stop playing advocatus diabolin.
