Early in 2012, Rodger Novak took a call from Emmanuelle Charpentier, co-discoverer of CRISPR-Cas91 - a DNA editing tool that has shot from the pages of academic journals to world renown in four years. "She asked me what I thought of CRISPR. I didn't understand," he recalls. "I said, 'What's CRISPR?'"
Charpentier outlined to him exciting results that were starting to come out of her lab, building on a paper she published back in 2011 in the journal Nature2 looking at how bacteria use the CRISPR-Cas9 system to cut up DNA from invading viruses. Back then it had seemed more of an academic research tool for chopping up DNA, but it was becoming clear to her that there were much wider applications - including altering the human genome - and she needed advice on how best to exploit them.
Charpentier and Novak met in the 90s when they were post-doctoral researchers at Rockefeller University in New York. An effusive and affable German, Novak chose to forge a career in the pharmaceutical industry while the quieter, more academically minded Charpentier pursued her research, ending up at Umeå University in Sweden, where she made her key discoveries. In his role as global head of infectious diseases at Sanofi's research and development labs in Chilly-Mazarin, France, Novak was the obvious person to call when Charpentier realised that her findings might have commercial value.
CRISPR-Cas9, usually known as CRISPR, is a two-part DNA-editing system that can be guided to almost anywhere in the genome of any organism. The CRISPR component itself is the biological equivalent of a satnav, comprising short stretches of RNA - the molecular "cousin" of DNA. These can be designed to match up with any DNA sequence and, once in place, CRISPR calls in Cas9, an enzyme that snips through the DNA at precisely the right spot. The gap is then filled with any other piece of genetic material, repairing, removing or entirely replacing what was there before.
The power of the technique was illustrated in a study reported in the journal Science at the end of 2015, in which researchers used CRISPR to replace the faulty gene responsible for causing the fatal muscle-wasting disease Duchenne muscular dystrophy in mice. It wasn't exactly a cure - the treated mice still weren't as strong as fully healthy animals - but it was an important proof of principle. And given that 20,000 babies a year are born with the condition worldwide, it was a powerful statement of hope for families as well as the research community.
A few months after that initial phone call in 2012, Charpentier and her University of California Berkeley collaborator Jennifer Doudna published their breakthrough research paper in Science, describing how CRISPR works and exploring its potential for precision genome editing. Based on his conversations with Charpentier ahead of publication - and the excitement in the research and industrial communities as word spread - Novak got in touch with VC and entrepreneur Shaun Foy to see if there was any commercial mileage in these gene-hacking tools. The answer was unequivocal. "[Shaun] checked it out and about four weeks later he called me saying, 'Listen, you have to leave your job - we're going to build a company,'" says Novak.
That company became CRISPR Therapeutics, originally founded in Switzerland as Inception Genomics in 2013 by Charpentier, Foy and Novak, who's now CEO. Starting with $25 million (£17m) in seed funding, Novak and his team are now sitting on more than half a billion dollars, much of it thanks to recent deals with pharma giants Vertex and Bayer. Signed in October 2015, the deal with Vertex released $105 million upfront, with more to come if CRISPR Therapeutics hits key targets in the development of treatments for blood disorders and cystic fibrosis. And in December 2015, the deal with Bayer brought in $300 million for research and development of therapies for a range of ailments including hereditary blindness3 and heart defects.
There's still a long way to go before CRISPR-based treatments are ready for testing. The tech works well on cells grown in the lab, and is showing promise in animal models of some human diseases, but correcting DNA errors in patients is a bigger challenge. At a new research facility in Cambridge, Massachusetts, the firm's scientists are starting to tackle the problem of delivering CRISPR's precision scissors - or, at the very least, cells that have had their genetic faults edited out using the technique - to the places in the body where they're needed.
Novak and his team have set their sights on delivering CRISPR directly into organs in situ. "One of the interesting organs we'd like to target is the liver," Novak says. "That's certainly the way to go. We're doing this and we're doing other things, but it's not a problem keeping our teams busy here because it's a tremendous amount of work."
Other companies - including Editas Medicine (co-founded by the Massachusetts-based Broad Institute's Feng Zhang, credited as a co-discoverer of CRISPR) and Intellia Therapeutics, co-founded by Charpentier's collaborator Jennifer Doudna at University of California, Berkeley (UCB) - are also staking out claims to this territory, sparking a legal battle between the two host institutions.
The patent rights are assigned to Zhang and the Broad, which licenses it to Editas, but this is being challenged by UCB. If UCB's successful, the rights could transfer to Doudna's team. Editas would then need to negotiate a licence from her at unknown cost. Despite this, Editas floated on NASDAQ in January 2016, raising more than $94 million.
"In academia, when there are great discoveries there are always people who claim something they shouldn't," Novak says. "There are US institutions which aggressively rewrite history. And that's something we as a company feel a responsibility for - to take care of [Charpentier] because we benefit from the fact she's our founder and the person who enabled the field." Her key experiments were in Sweden, where the law recognises "professor's privilege": the person who made a discovery, rather than the institution, owns the IP. "We shouldn't forget that since [she] is one of the key inventors of this patent, she's in a very special situation as the owner of this IP," Novak explains. "I think it's fair to say without her work we wouldn't have any CRISPR companies. We wouldn't have anything."
- Doudna JA and Charpentier E, 2014. "The new frontier of genome engineering with CRISPR-Cas9," Science 346:1258096
- Jinek M et al, 2014. "A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity," Science. 337:816-213. researchgate.net/publication/275517326
- Ledford H, 2015. "Success against blindness encourages gene therapy researchers," Nature 526, 487-488
Updated 24/6/2016 to remove reference to Spark Therapeutics. WIRED incorrectly stated Spark's study into using viruses to deliver replacement genes into eyeballs showed only short-term results. A three-year study has actually shown its therapy has a sustained effect.
This article was originally published by WIRED UK
