The waning enthusiasm for RNAi technology can be attributed largely to the unintended immune response to drugs that essentially resemble many viruses (double stranded RNA triggers an immune response which is widely believed to be a defense against viruses). Ironically, if successful, RNAi could be used effectively to treat patients with pathogen infections.
RNAi, a Nobel Prize-winning technique to turn genes off and, has not integrated into treatment methods as many had imagined despite billions of dollars of investment. The New York Times reports that many pharmaceutical companies are now losing their enthusiasm for RNA interference (RNAi)—Roche, Pfizer, and Abbott Laboratories have all shut down their RNAi projects within the last year.
One of the major problems with RNAi is that although drugs effectively shut down genes, it is difficult to deliver the drugs to the correct cells. Often, RNA is broken down in the bloodstream and if it does reach its targeted cell it has difficulty entering the cell. Another problem is that double-stranded RNA pieces can trigger immune responses (perhaps because they resemble viruses). No solution to these problems is apparent, so drug companies have shifted their focus to techniques that seem closer to producing marketable drugs.
RNAi is a natural occurrence in cells. When a cell senses a double strand of RNA, it silences any genes with the corresponding sequence of bases—a process largely thought to be a defense against viruses. To harness RNAi for drug production, drug companies intend to silence any disease-related gene by synthesizing a short complement of double-stranded RNA—small interfering RNA (siRNA). Such a technique could be used to silence a gene associated with high cholesterol or a gene needed by a pathogen to survive.
Several solutions to RNA delivery have been proposed and tested; however, little data exists as to whether or not these techniques have been successful. Chemically altered RNA survives in the bloodstream and can avoid immune detection. RNA packaged in lipid particles target liver-related diseases because lipids naturally accumulate in the liver. For other targets in the body, scientists are now experimenting with attaching specific “stamps” to the RNA to deliver it to the correct destination. Many of these techniques, however, do impose significant side effects.
“Stamped” RNA has shown promise in HIV clinical trials. By using an aptamer—a piece of RNA that twists into a particular shape—scientists have shown that RNA could be delivered to HIV-infected immune cells.
The promise of RNAi is that in theory it can shut down a gene to prevent a “troublesome” protein from being produced. However, alternatives have gained more steam in recent years. Monoclonal antibodies, antisense, or techniques to block protein action or binding affinity have been proven effective for many diseases in recent clinical trials.