GARTNER, an American consultancy, has a simple yet elegant way of describing the life of a promising new technology. First, it is talked up to a peak of inflated expectations. Then it falls into a trough of disillusionment. After that, if it survives, it begins climbing the slope of enlightenment. Finally, it reaches the plateau of productivity.

In the world of biotechnology CRISPR/Cas9 (see article), is still ascending towards peak expectations. True to the Gartner hype-cycle, though, an earlier star, RNA interference, or RNAi, is well and truly in the trough. The chart alongside, of Google searches for the two technologies, shows this. The question is, can RNAi climb the slope of enlightenment to become a productive and useful technology? And the answer looks increasingly likely to be “yes”.

Like CRISPR/Cas9, RNAi is based on a bacterial response to viral infection. RNA is a molecule that is chemically similar to DNA, and does many jobs in cells. All these jobs, though, use single-stranded versions of RNA, unlike the double-stranded DNA in a cell nucleus. Double-stranded RNA does exist naturally, but it is found only in viruses. For this reason, RNAi recognises double-stranded RNA and destroys it.

When RNAi was discovered, it looked tailor-made to be the basis of a new class of drugs. One of RNA’s main jobs is to carry information from genes in the nucleus to protein factories in the rest of the cell. If messenger molecules could be destroyed this would reduce or eliminate the proteins they produce. Since proteins, in the guise of enzymes, signalling molecules, ion channels and so on, regulate all cellular processes, the range of diseases to which RNAi-based drugs might be applied seemed boundless.

Such drugs, known as small interfering (“si”) RNAs, are short double strands of the molecule. This is enough to fool the RNAi system into thinking a cell is under attack. The drug works because one strand of each siRNA is complementary to the messenger strand that is the object of interest. The RNAi system pulls the siRNA strands apart and uses the complementary strand to seek out and bind to the target messenger, thus disabling it. The result is, in principle, a precise means of knocking out proteins involved in particular disease.

Drug companies duly jumped aboard the RNAi bandwagon. In 2006 Merck, an American giant, paid $1.1 billion for Sirna Therapeutics, a biotechnology firm reckoned to be a leader in the field. Roche and Novartis also made big investments around the same time. RNAi, it seemed, was going to take the pharmaceutical world by storm.

But siRNAs, so attractive in theory, proved impossible to tame in practice. Roche ended its work in 2010. Novartis and Merck followed suit in 2014. Nevertheless, a clutch of biotechnology companies are still working on the idea, and some of them now think they have cracked it. Chief among them are Alnylam and Dicerna, both of Cambridge, Massachusetts. These firms have, they believe, overcome one of the problems that caused RNAi to fall so deep into the trough of disillusionment—getting siRNA molecules across cell membranes to where they are needed.

The firms have done that in two ways. One is by encasing the RNA in fatty capsules less than a micron across. These capsules are easily absorbed by liver cells, and the liver is a target-rich environment for RNAi-based therapies. The other (a method that is the subject of a legal dispute between them) is to attach the siRNA molecules to other molecules that are readily taken up by liver cells.

According to Alnylam’s boss, John Maraganore, his company has seven siRNAs in clinical trials. The most advanced of these are two intended to combat TTR-mediated amyloidosis, an inherited disorder. In this case the siRNA involved knocks out the messenger from the mutant gene which causes the disease. These two molecules are in phase three of the clinical-trials process—the one in which a drug’s broad efficacy is assessed after it has passed earlier safety trials.

But, though bad for those who suffer from it, TTR-mediated amyloidosis is rare. The treatment in the firm’s pipeline that has the greatest market potential is directed against low-density lipoproteins (LDLs), the “bad cholesterol” which increases someone’s risk of heart disease.

In this case the target is PCSK9, a protein that regulates production of certain receptor molecules found on the surfaces of liver cells. These receptors pluck LDLs from the bloodstream for disposal. Less PCSK9 means more receptors and hence, the theory goes, lower LDL levels.

For its part, Dicerna hopes to block messages sent by two genes called KRAS and MYC—or, rather, by mutated versions of these genes. The genes in question are known as oncogenes, for when they go wrong they can lead to the growth of cancers. At the moment, neither KRAS nor MYC is regarded as “druggable”. In other words, not only are no drugs available, but no good way of developing them exists. Dicerna’s researchers intend to change that with their tailor-made siRNA.

In Australia, meanwhile, Benitec Biopharma of Sydney is developing another way of getting siRNAs into cells. This is to encourage those cells to make the molecules themselves. To do so means integrating genes which encode the siRNA in question into a cell’s nucleus. For this, Benitec employs viruses engineered for the purposes of gene therapy. The result, which the firm calls DNA-directed RNAi, is now being tested on Hepatitis C, a disease that kills about 500,000 people a year. If that works, treatments for other illnesses should follow.

Whether any one of these approaches will actually succeed in climbing the slopes of the plateau of productivity remains to be seen. But they do have promise. RNAi, less hyped than it once was, may still have a bright future.