eGenesis bets on CRISPR to domesticate pig organs for safer xenotransplantation

Boston-based eGenesis recently received $38 million in Series A financing to develop a safer xenotransplant. Founded by research superstar and serial entrepreneur George Church and former Church lab scientist Luhan Yang, the company is using CRISPR gene editing to make pig organs suitable for human transplantation.

The need is great. Around 120,000 people are on an organ waiting list, but only 31,000 transplants were performed in 2015, according to organdonor.gov. As many as 22 people die each day waiting for a donor organ.

Luhan Yang Headshot

Luhan Yang, eGenesis cofounder

Advertisement

“I think those numbers are smaller than reality,” says Yang, the company’s chief scientific officer, in a phone interview. “If we look at the number of patients who suffer from organ failure in this country, there are over three million.”

Xenotransplantation could solve the problem, but the practice has a long legacy of failure. As recently as the 1990s, a number of companies were working on it, but the dual problems of immune rejection and porcine endogenous retroviruses scuttled those projects.

“If you culture pig cells with human cells, the viral genome will jump from the pig to the human genome, similar to how HIV passed from non-human primates to humans,” said Yang.

But CRISPR could change that. In 2015, the Church lab published a landmark paper in Science detailing how they used CRISPR to disrupt 62 viral gene copies.

“From a science basis it was remarkably exciting when George and colleagues published how you can CRISPR 60-some genes at once, which was kind of the Olympic record at the time and probably still is,” said Eric Topol, who directs the Scripps Translational Science Institute in San Diego, in a phone interview. Topol has no affiliation with eGenesis.

While the paper produced fireworks, there’s still a long way to go for eGenesis. It’s unclear how many genetic modifications the team will have to make before porcine organs become tolerable in human patients. And though it’s theoretically possible to make organs more compatible than the human counterparts, that is not the company’s goal.

“Our measure of success in the near term is if we can create the organs so that a conventional immunosuppression regimen can be used after transplantation,” said Yang.

Funded by Biomatics Capital, ARCH Venture Partners and others, the recent financing will help eGenesis develop solid proof of principle. They hope to begin preclinical studies in the next three years.

Like gene therapy, xenotransplantation is experiencing a renaissance. United Therapeutics, in collaboration with Synthetic Genomics, is also developing pig organs for transplant. Bioprinting companies like Organovo may also be working their way towards transplantable organs.

While major technical hurdles remain, the rise of CRISPR makes them seem surmountable. And for eGenesis, having George Church on the team cannot hurt.

“Never underestimate George,” said Topol. “He is one of the most brilliant scientists I’ve ever known, and he has a strong sense that this is going to play.”

Photo: wildpixel, Getty Images 

Allergan and Editas announce $90M CRISPR deal

The CRISPR patent interference case was newsworthy not because of the dispute, but because of the potential of the underlying technology.

As that uncertainty begins to clear, it’s time to get back to the scientific promise.

On Tuesday, Allergan Pharmaceuticals and Editas Medicine announced a new “strategic research and development alliance,” which grants Allergan exclusive access and an option to license up to five investigational programs for specific eye disorders.

Editas will receive an upfront payment of $90 million, with the potential to earn more if certain milestones are reached.

At the heart of the deal is Editas’ lead program for Leber congenital amaurosis (LCA), a family of rare, inherited retinal dystrophies. LCA is the most common cause of inherited childhood blindness, with a global incidence of two to three per 100,000 live births. Symptoms typically begin within the first year of life, leading to substantial vision loss and blindness.

Across the 13 subtypes identified, scientists have isolated disease-causing mutations in at least 14 different genes. Editas has focused its efforts on LCA10, a subtype driven by a defect in the CEP290 gene that accounts for some 20-30 percent of cases.

As a gene-editing technique, CRISPR could theoretically be used to correct the faulty gene early in life, lessening or preventing the dystrophy (wasting) of the retina and the resulting loss of vision. If the fundamental mutation is corrected, there’s a hope that the response could last for the rest of the patient’s life.

Whether or not that will eventuate remains to be seen. Based in Dublin, Ireland, Allergan has a well-established portfolio of ocular therapies. But all five Editas programs are preclinical and the CRISPR field only goes back four or five years.

Editas seems confident that the new partnership will help it achieve long-term success.

“Working together with Allergan through their Open Science R&D model significantly enhances our ability to develop genome editing medicines to help patients with serious eye diseases,” said Katrine Bosley, president and CEO of Editas in a joint news release. “This alliance is highly aligned with our strategy to build our company for the long-term and to realize the broad potential of our genome editing platform to treat serious diseases.”

Several weeks ago, Boston, Massachusetts-based Exonics Therapeutics launched with $5 million in seed funding from CureDuchenne Ventures, the investment arm of a non-profit Duchenne muscular dystrophy (DMD) advocacy group. While the research is early-phase, the ultimate aim is to deliver a single treatment to DMD patients, correcting the faulty gene that drives their debilitating disease.

Of note, Allergan has scooped up licenses pertaining to both CRISPR/Cas9 and CRISPR/Cpf1. The latter was developed through the work of Feng Zhang and collaborators at the Broad Institute, MIT and Harvard — the institutions that Editas licenses its technology from. Both enzymatic approaches have distinct pros and cons, which means scientists would ideally have access to both.

Photo: Jay_Zynism, Getty Images