Gene therapy, make way for gene “editing.”
Today, three of Boston’s biotech startup creators—Polaris Partners, Third Rock Ventures, and Flagship Ventures, have banded together to create a new, Cambridge, MA-based startup called Editas Medicine.
It’s a sizable bet. The three, with the help of Partners Innovation Fund, have plunked down a $43 million Series A into the new startup, which has ambitious plans to create an entirely new class of drugs based on what it calls “gene editing.” The idea is similar, yet different, from gene therapy: Editas’ goal is to essentially target disorders caused by a singular genetic defect, and using a proprietary in-house technology, create a drug that can “edit” out the abnormality so that it becomes a normal, functional gene—potentially, in a single treatment.
“I would think of this as really the potential for a whole new class of therapeutics,” says Kevin Bitterman, a principal at Polaris and Editas’ interim CEO. “We can go in and, without really any limitation since it’s a programmable system—we can target any gene in the genome and theoretically fix a mistake, remove a gene, or modulate expression in a very targeted way.”
Editas, which has been operating in stealth mode for a few months, is being tight-lipped so far about how it wants to apply this. Bitterman wouldn’t disclose, for instance, what molecular targets the company plans to initially focus on, which types of diseases it wants to go after, how much of the $43 million Editas has access to off the bat, or even what kind of intellectual property Editas is amassing to protect itself from competitors. But it’s been toiling away behind the scenes developing a platform based on the work of five of the most prominent researchers in the field: Feng Zhang, of the Broad Institute of MIT and Harvard; Harvard University genomics expert George Church; Jennifer Doudna, a Howard Hughes Medical Institute investigator and a professor at the University of California in Berkeley; David Liu, another Howard Hughes Investigator and Harvard professor; and Keith Joung, a pathologist at Massachusetts General Hospital as well as a Harvard professor.
It’s also assembled a board of Third Rock (Alexis Borisy), Flagship (Douglas Cole), and Polaris (Terry McGuire) members, and three executives to lead the effort initially: Bitterman, Third Rock partner Lou Tartaglia (interim chief scientific officer), and Alexandra “Sandra” Glucksmann (interim chief operating officer), a former co-founder of Cerulean Pharma, another Polaris portfolio company.
Editas’s big plan is to cure genetic diseases by engineering a process that mimics the adaptive immune system of bacteria. It’s long been known, for instance, that two pieces of bacterial cellular machinery—CRISPR (clustered, regularly interspaced palindromic repeats) and an enzyme called Cas9, or CRISPR-associated protein 9—help bacteria form an adaptive immune system by essentially memorizing the appearance of an invading virus and equipping themselves to fight that virus off if it comes back again.
Specifically, when a virus infects a bacterium, the bacterium’s CRISPR reads the virus’s DNA, memorizes it, and incorporates it into its own genome. This produces RNA that Bitterman says serves as “a guide” that can recognize the virus when it comes back to infect the bacterium again, alert the Cas9 enzymes, and show them where to go. Those Cas9 enzymes then fend off infection, rendering the bacteria immune to that specific virus.
Editas says that its founders have uncovered a way to recreate this type of process so it can be used to “edit”—remove, fix, or otherwise—genes in human cells. Instead of there being an RNA guide that recognizes viral DNA, and sends Cas9 enzymes out to fight it, Editas would engineer its own RNA guide whose job is to recognize a specific genetic sequence—say, a corrupt or mutated gene—and transport the Cas9 enzyme to the site of the problem, where it can correct the genetic error. Bitterman says, to his knowledge, Editas is the only company so far attempting to use the CRISPR/Cas9 system to create drugs.
Editas’ founders also have another way of doing this, utilizing enzymes called transcription activator-like effector nucleases, or TALENs, but the company isn’t saying in which cases it might want to use one method over the other as of yet—just that it’s a second potential tool in the toolbox.
Though gene editing may sound similar to gene therapy, Bitterman says that the two approaches are different. Gene therapy uses engineered viruses to deliver healthy genes into a cell to replace faulty or missing ones, and is more limited.
“Gene therapy expresses a fixed copy of a broken gene,” he says. “The difference is the very precise targeting, the ability to actually impact and change or edit a gene in the genome…and to make that very specific change and nothing else.”
Editas, in theory, could use this system to create a drug that could cure any number of genetic diseases via a one-time fix, and be more flexible than gene therapy or other techniques used to cure a disease on the genetic level. But even so, the challenges, just like gene therapy, are significant. Editas has to figure out a way to safely and effectively deliver a gene-editing drug into the body, something Bitterman acknowledges is one of the big hills the company has to climb. Likely, the drugs will be delivered via injection.
“We can leverage a lot of the work that’s been done in areas like gene therapy and RNA [interference] in terms of the delivery approaches—we don’t need to reinvent the wheel,” he says. “Delivery is something we’re thinking a lot about, [and it’s] an area that our three firms and the team that we’re building knows well.”
Of course, despite its credible backing and lofty goals, Editas is in its infancy and is thus totally unproven. The best proof it has to date is evidence by its founders that the process can be engineered to work in petri dishes with mammalian cells.
Editas has five full-time employees (the goal is to get to 30 workers by the end of year two), doesn’t have an office yet, and still hasn’t decided exactly which diseases it’ll target first. The cash will be used to get the platform ready for prime time, and build out its scientific and operational team so Editas’ technology will be ready to go when the company has a better sense of what its priorities will be in clinical trials.
“It’s really time to step on the accelerator,” Bitterman says.