RNAi, Don’t Be a Hater

It’s easy to join the “RNAi doesn’t work” bandwagon these days.  Roche and Merck have all but given up hope on the space, and partnering talks for existing RNAi startups have ground to a halt.  But, people should be reminded that pharma investment interests go in cycles, and well, RNAi might just be in a down cycle as opposed to being a write-off.

That being said, should RNAi really be in a down cycle?

Many of us haven’t given up hope on the promise of RNAi, a relatively new science that was only first discovered in 1998.  In a short amount of time, RNAi has established itself as a staple of research labs and become the go-to assay for modulating gene expression patterns.  While academic researchers typically do not have to worry about tissue specificity, stability, etc., the ubiquitous usage of RNAi illustrates the promise of the technology.  

In some respects it is not a surprise that pharma companies and startups have struggled to commercialize RNAi.  Many of the mechanisms and molecules associated with RNAi processing have only recently been discovered.  Such discoveries should empower researchers to invent new methods for RNAi delivery and tissue selectivity.

Al Doig of Insight Pharma Reports recently compared the current state of RNAi drug development to that of monoclonal antibodies in the early 1990s.  Al notes,

“It was a 1975 publication describing the technology for generating MAbs, for which the authors received a 1984 Nobel Prize, that ignited interest in the possibility of MAb therapeutics. In the 1970s and 1980s, MAb technology represented great science, and biotechnology and pharmaceutical companies were excited at the prospect of developing MAb drugs. However, the development of MAb-­based drugs lagged far behind the science. The first MAb drug, Johnson & Johnson’s Orthoclone OKT3, was approved in 1986, albeit with limited applicability. Interestingly, there were no other approved MAb drugs until 1994 and the “avalanche” of MAb drug approvals didn’t begin until 1997.”

To put that timeline in perspective, when compared to MAbs, the avalanche of RNAi drugs should come sometime around 2020.  There are numerous great startups, many of which are university startups that are poised to set off that avalanche: 

• Alnylam – Scripps, Rockefeller, MIT
• Tekmira – University of British Columbia
• RXi Pharmaceuticals – University of Massachusetts
• Calando Pharmaceuticals – Caltech
• Silence Therapeutics – spinout of Ribozyme Pharmaceuticals (University of Colorado)
• Quark Pharmaceuticals – licensed core technology from Silence Therapeutics
• Dicerna - City of Hope

I prefer to think of RNAi as in a lull right now.  It has gotten past the initial hype and enthusiasm, and now people are performing the long, arduous, and non-sexy task of making the technology work so that it ultimately can have clinical utility.  Positive clinical data from any of these companies should provide enough momentum for RNAi to become hot again.