John Maraganore

Interfering with disease: a progress report on siRNA-based therapeutics

RNA interference (RNAi) quietly crept into biological research in the 1990s when unexpected gene-silencing phenomena in plants and flatworms first perplexed scientists. Following the demonstration of RNAi in mammalian cells in 2001, it was quickly realized that this highly specific mechanism of sequence-specific gene silencing might be harnessed to develop a new class of drugs that interfere with disease-causing or disease-promoting genes. Here we discuss the considerations that go into developing RNAi-based therapeutics starting from in vitro lead design and identification, to in vivo pre-clinical drug delivery and testing. We conclude by reviewing the latest clinical experience with RNAi therapeutics.

Community crystal gazing

A selection of individuals from the biotech ecosystem give their views on the challenges facing the sector over the coming years.

First rounders: John Maraganore

401 worked with ARCH Venture Partners to seed, found and launch Denali with its monstrous

Erratum: Community crystal gazing

217-million series A round. Working with builders like Atlas and ARCH means F-Prime “probably helped supercharge” the trend of high A rounds, he says, adding that “most of the groups we work with want to build things that are real.” But investors follow the money, and certainly some in biotech are there less for the science and more for the returns. These days All of this is good news for biotech. There is always concern when the sector is awash in money that some of the bets are bad, and when they implode, the funding environment will collapse with it. But science and money are intertwined, and biotech needs both. The 154 A rounds in 2017 are 154 new companies chasing down disease, and they weren’t there a year ago. Stephen Knight, president and managing partner of F-Prime Capital Partners, it’s not easy to know who is who. Perhaps the crossover investors and hedge funds that are newly playing with company creation are doing it because they understand the benefit it can bring to patients. Or, perhaps they want the returns early-stage building can bring. “That’s one of those things,” Knight says. “When the tide goes out, we’ll find out.”

A status report on RNAi therapeutics

Nat. Biotechnol. 34, 276–283 (2016); published online 10 March 2016; corrected after print 31 March 2016 In the version of this article initially published, Stanley Crookes name was misspelled as “Crook” in the author list. The error has been corrected in the HTML and PDF versions of the article.