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There is mounting evidence that RNAi, once hailed as a panacea for the pharmaceutical and biotechnology industries, may not be all that it was claimed to be. Yes, there are several new RNAi drug candidates in late stage clinical development but it isn’t clear, at this point, whether any of these products will ever make it to market. Companies like Allergan, Alnylam, Opko Health and Merck, which recently bought the RNAi company Sirna Therapeutics for $1.1 billion, have invested hundreds of millions of dollars and literally “bet the farm” on RNAi therapeutics.
The use of DNA and RNA as therapeutics is not a new or novel idea. Isis Pharmaceuticals, a pioneer and champion of oligonucleotide therapeutics, has only be able to bring a single, oligonucleotide-based product to market in the past 20 years. Ask any Isis executive and they will tell you that turning DNA or RNA into drugs is a challenging process that is fraught with many difficulties. Most notably, there are bioavailability, delivery and target specificity hurdles that most be over come before the utility of these drugs as therapeutic agents can be realized. That said the attractiveness of these molecules as therapeutics (and perhaps their real danger) is the simplicity and elegance of their mechanism(s) of action. Most scientists tend to “fall in love” with elegant and parsimonious solutions to complex processes—why would we not, they are type of discoveries that we all train and live for! And, as many of us know, when people “fall in love”, there is a tendency to overlook or not notice warning signs that things may not be as they seem.
The scientific community fell quickly and deeply in love with RNAi soon after the first papers appeared touting its benefits and possible therapeutic applications. Scientists were so convinced and confident about RNAi that they induced the financial community to invest billions of dollars into the emerging technology. The love and affection for RNAi reached its pinnacle in 2006 when two scientists, who played a crucial role in discovering its mechanism of action, won the Nobel Prize. Since then, the harsh realities of RNAi drug development have begun to be realized by companies that invested in the technology.
I have been around long enough to understand that there are fads in science. In the mid 1990s it was combinatorial chemistry, in the late 1990s it was genomics, proteomics and computational chemistry and in the 2000s it is RNAi. Don’t get me wrong–all of these technologies have helped to advance science and provide researchers with sophisticated tools that have helped to expedite the drug discovery and development process. That said, none of these technologies, by themselves, yielded the plethora of new medications or therapeutics that their advocates promised. Industry veterans know that there are no easy solutions or panaceas in drug discovery and development. The process is inherently time-intensive, painstaking and tedious. And, despite what we scientists want to believe in our “heart of hearts,” there are no guarantees that simplicity and elegance will translate into safe and effective medications.
Until next time….
Good Luck and Good Job Hunting!!!!!!!!!!
A team of scientists from the UK report in this week’s edition of Nature that they were able to induce the formation of ribonucleotides using ribose, phosphate and the bases adenine, uracil, guanine and cytosine and environmental conditions that may have been present in the early history of the Earth. This had been a fundamental but elusive step in the early evolution of life on Earth. 
Vincent Racaniello, an intrepid virologist and 
