In the US alone, there are over 10 million men, women, and children diagnosed with some type of cancer (US National Cancer Institute, 2002). Depending on how advanced their cases may be, they are all going through treatment, whether its chemotherapy, radiation or surgery, that leaves their bodies bruised, exhausted, and badly damaged. Even after the painful ordeal of treatment, the chances of survival for some may still be poor. But now there may be a hope, a new method of attack that can turn off the gene that is expressing that particular disease. It’s as easy as flicking off a light switch.
From Big Pharma to Small Biotech, that 'light switch' is being sought after in the new research craze called RNAi (also known as RNA-mediated interference). Termed such by Craig C. Mello and Andrew Fire in their 1998 Nature paper, for which in 2006 they received the Nobel Prize in Physiology or Medicine, RNAi exploits a cell’s normal mechanism of gene expression. When a virus attacks a cell, it introduces its own RNA into the cell and forces the cell to use its own process of translation to make multiple copies of viral RNA and viral proteins.
But when the virus is copying itself, it is a double stranded sequence, unlike the single stranded RNA that occurs naturally in the cell. The process of RNAi uses this distinction to search out the double stranded RNA, chop it up into small pieces, and then go in search of matching sequences that may still be in the cell. As it finds matches, it binds to that viral RNA strand and blocks the viral RNA protein production; hence, halting the virus in its attack. So those clever men and women behind the lab benches have come up with a method to exploit this mechanism. By artificially introducing a double stranded RNA from a diseased gene into a cell, the cell’s normal RNAi process silences that disease gene, just as it would silence a naturally invading virus. Then it goes after everything in the cell that exhibit that diseased sequence; consequently, impeding the disease from development.
From petri-dishes, to lab animals, to first human volunteers in late 2004, researchers have been trying to figure out radical new ways to manipulate a patient’s own RNAi immune response to fight hundreds of diseases. Visualize that just by turning off a gene like a “light switch,” illnesses as severe and debilitating as macular degeneration, respiratory infections, hepatitis, Huntington’s disease, Alzheimer’s, HIV, and yes, even cancer, could be shut off from progressing.
Some of the names that are known to be working with this technology include the big boys of Big Pharma: Novartis (NYSE:NVS) and its collaboration with Alnylam (NASDAQ:ALNY), not to mention Alnylam’s own federal government contract; Merck (NYSE:MRK) and its partnership with Alnylam and acquisition of Sirna Therapeutic for $1.1 billion; Pfizer (NYSE:PFE) and Quark Biotech Inc’s licensing agreement for RTP-801; AstraZeneca (NYSE:AZN) and Britain’s Silence Therapeutics $400 million research pact; Roche (OTCPK:RHHBF) and its last month announcement of a major alliance with Alnylam worth $331 million plus; and Bristol-Myers Squibb’s (NYSE:BMY) payment of $192 million to Isis Pharmaceutical (NASDAQ:ISIS) for exclusive access to its PCSK9 research program. The smaller Isis Pharmaceuticals, one of the first pioneers in RNAi drugs, and biotech CytRx Corp (NASDAQ:CYTR) even have separate divisions devoted solely to siRNA chemistry and formulation, with other companies like Nastech (NSTK) licensing intellectual property and technology for their own research and development.
The next few years will start to tell the story of whether this remarkable innovation can succeed clinically. Though RNAi research is in its infancy, as there are still many hurdles on the horizon, I believe that the sun has only begun to rise into the wide blue sky of RNAi.
Disclosure: The author of this article has a long position in AZN and is an employee of Roche