The following article is part of our list of 2016 Game Changers. Look for full coverage of all 46 honorees on Friday.
A trio of startup companies rooted in the local life-sciences community is focusing on a task long seen as the Holy Grail of drug discovery: fixing broken genes.
Rival firms Editas Medicine Inc., Intellia Therapeutics Inc., and CRISPR Therapeutics are all pioneering an emerging technology known as gene editing. They use a new scientific tool called CRISPR-Cas9 that holds the promise of curing thousands of genetic diseases by cutting out and revising, removing, or repairing DNA, the building block of life.
“It’s a spectacular challenge,” says Katrine Bosley, chief executive of three-year-old Editas, which went public with its $94.4 million initial offering earlier this year. “The sense of urgency is very high. So is the sense of wanting to get it right. We have a long path ahead of us.”
In a biopharmaceutical sector constantly being reshaped by new science, from tissue engineering to immuno-oncology, genome editing is viewed by many as the rare breakthrough that could spawn numerous companies and treatments in the coming years.
“They’re just beginning to figure out the applications,” says Ellen Licking, a senior life-sciences analyst in the San Jose, California, office of accounting and consulting firm EY (formerly Ernst & Young). “If you’re talking about tools, this could fundamentally change how scientists attack [disease] targets in the research and development world. They’re looking at therapies that are highly valuable in the marketplace and will be relatively easy to deliver to diseased tissues.”
Editas, cofounded by Harvard geneticist George Church, has set its sights initially on a rare eye disease called Leber congenital amaurosis, partly because scientists have identified the genetic defect but also because the eye is relatively easy to reach for a gene-editing procedure.
Intellia, which raised $108 million in its own IPO earlier this month, is developing treatments for cancer and liver disease. CRISPR Therapeutics is targeting the blood disorders sickle cell disease and beta thalassemia.
But the new field has given rise to almost as many questions as therapeutic targets. The intellectual property behind the scientific tool used by all three companies was originally developed in molecular biology labs at the Broad Institute of MIT and Harvard, the University of California, Berkeley, and the University of Vienna. That has led to a high-stakes patent dispute. Since Editas has licensed its technology from the Broad, while Intellia and CRISPR Therapeutics have licensed theirs from UC Berkeley and the University of Vienna, a case now before the US Patent and Trademark Office could influence the race to market.
Genome-editing pioneers admit to an abundance of caution. They recall the case of an 18-year-old patient with a rare metabolic disease who died in a 1999 clinical trial using another fledgling medical approach, gene therapy, setting the field back more than a decade. They are chastened, too, by the initial burst of enthusiasm around a gene-silencing technology called RNA interference that slowed to a long slog as science moved into real-world development.
The would-be gene editors also must navigate a new round of ethical questions, including calls for a moratorium on tampering with human DNA — even to repair genetic defects — for fear that “rewriting the book of life” could open the door to designer babies.
But that has not stopped investors from piling on. More than $1 billion in venture capital financing has been plowed into gene-editing companies over the past two years, according to the Boston Consulting Group.
Larger biopharma companies also have been making big bets on the field. Boston’s Vertex Pharmaceuticals Inc. and Bayer AG of Germany have forged partnerships with CRISPR Therapeutics. Editas has an alliance with Juno Therapeutics Inc. of Seattle, while Intellia is collaborating with the Swiss drug giant Novartis AG, which bases its global research operation in Cambridge, and biotech Regeneron Pharmaceuticals Inc. of Tarrytown, New York.
Other companies, ranging from Sangamo BioSciences Inc. of Richmond, California, to France’s Cellectis, are working on different types of gene editing. But within the research field, CRISPR-Cas9 is considered the superior method and is being widely adopted worldwide.
“It’s easy to use in labs,” says Michelle Hoffmann, senior vice president for Boston consulting firm Back Bay Life Science Advisors. “You can make precise genetic edits, and it has a lot of promise clinically. The challenge is figuring out how to deliver it safely and efficiently.”