The 1998 discovery of the technique known as RNA interference (RNAi) set off a race among drug and biotech companies to harness the power of RNA silencing for therapeutic purposes. But that momentum appeared to grind to a halt recently when several major pharmaceutical companies began abandoning RNAi, which uses short snippets of RNA to selectively silence the expression of specific genes. The Swiss drug giant Roche, for example, announced in November 2010 that it was ending all RNAi work after it had already invested more than $500 million on the technology; in February 2011, New York's Pfizer followed suit, shuttering its RNAi drug discovery program.

Less than four years later, though, big pharma's enthusiasm for the therapeutic approach seems to be building once again. On 9 January, Roche unveiled a deal with Denmark's Santaris Pharma to collaborate on RNA-silencing medicines. Four days later, Genzyme, the biotech arm of the French heavyweight Sanofi, wrote a $700 million check to Alnylam Pharmaceuticals, a developer of RNAi drugs based near Genzyme in Cambridge, Massachusetts. That investment—which sent Alnylam's stock price rocketing up 40%—gives Genzyme a 12% stake in the company.

RNAi has “come of age,” says Michael King, a New York-based biotechnology analyst with JMP Securities, an investment banking firm. Alnylam in particular has “shown that RNAi can be a useful therapeutic,” says Alan Carr, an analyst at Needham & Company in New York, citing the company's recent clinical trials of RNAi therapies for high cholesterol (Lancet 383, 60–68, 2014) and a rare inherited disorder known as transthyretin-mediated amyloidosis (N. Engl. J. Med. 369, 819–829, 2013). “So it seems to me that it was a matter of time for pharma to realize that it's time to revisit [RNAi].”

King describes the partnerships as “win-win” ventures for all parties involved. In the case of the Genzyme-Alnylam alliance (which builds off of a partnership the two companies initially formed in 2012), Genzyme gains increased access to the RNAi-based medicines in Alnylam's clinical pipeline. In return, Alnylam can lean on the rare disease expertise of Genzyme and the global reach of Sanofi to identify additional patients willing to pay for the company's drugs. “That's the true strength of this partnership,” says Marko Kozul, an analyst at Leerink Partners in Boston.

Yet, not all pharma companies are showing the same renewed interest in RNAi. Merck had long bucked the industry trend by keeping skin in the RNAi game. On 12 January, however, the New Jersey drug giant revealed that it was selling off its RNAi-focused subsidiary—San Francisco–based Sirna Therapeutics—and various associated assets.

The buyer was Alnylam. The price paid: a mere $175 million, well below the $1.1 billion Merck spent to acquire Sirna in 2006. That cut-rate sticker price could be a real bargain for Alnylam, but it may also be a sign that the latest wave of enthusiasm for RNAi therapeutics is more tempered than in the not-so-distant past.