A: Precision’s ARCUS genome editing technology is a proprietary, non-CRIPSR platform that has applications across cell therapy, gene therapy, and agriculture. We are able to edit everything from plants to primates, so prioritizing projects is an imporant part of what we do. In agriculture, we are focused on enhancing nutritional value and fortifying at-risk crops. In medicine, we are developing ex vivo gene edited cell therapies that fight cancer as well as in vivo gene editing therapies targeted to the liver and the eye.

A: Our lead product is an off-the-shelf CD19 CAR T to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). This is made from the T cells of healthy donors, which we edit in two ways – first, we add a receptor that targets cancerous cells and second, we knock out a receptor that mediates graph-versus-host interactions to eliminate the need for donor-patient matching. Using this method, we can generate hundreds of vials of CAR T cells from a single manufacturing run to treat patients when and where they need it. Another even newer area of genetic medicine we are excited about is in vivo therapeutic genome editing. Because the ARCUS editing platform works effectively and reproducibly in non-human primates and other large animal models, we can look beyond basic mouse studies and begin using editing to therapeutically suppress or correct expression in models that inform the development of human therapeutics.

A: I am the CSO of Precision BioSciences and also a co-founder, along with Matt Kane (our CEO) and Jeff Smith (our CTO). We started the company back in 2006, soon after Jeff and I created the earliest version of ARCUS, but I’d already been working in genome editing for almost 10 years by then. I have studied and worked with zinc finger nucleases, TALENs, and CRISPRs, but have always preferred the homing endonuclease (aka meganuclease), which ARCUS is based on, for therapeutic applications. The time and effort our team at Precision has put into this platform has been nothing short of heroic, and now we are seeing the pay off as we progress toward clinic in both cell and gene therapy.

A: The field has made real headway into editing human cells in vitro, particularly for CAR T. Several new gene edited CAR T therapies are either in the clinic or expected to enter the clinic within the next year. In vivo therapeutic editing isn’t quite as far along but there are a couple of ZFN-based therapies in very early clinical studies. We recently published a study in collaboration with the Wilson lab at Penn demonstrating, I think for the first time, high-efficiency, long-term in vivo editing in primate liver. We knocked-out the PCSK9 gene in several animals, resulting in therapeutically-relevant reductions in LDL cholesterol that are stable now well into the second year of the study. We think the study provides a blueprint for developing additional liver-targeted in vivo editing therapies using the ARCUS platform.

A: For the field at large, translating our success from the bench to the bedside has been challenging. Gene editing has revolutionized biomedical research, but creating bona fide in vivo therapies is a big ask and the place everyone in this space would like to go. This means creating new medicines able to cure disease by editing patient DNA at the organ or tissue of interest, preferably with a single treatment. It’s the “holy grail” of genome editing and what I have been working toward my whole career. We’re close but we aren’t there yet. The transition to large animal models – getting beyond mouse work – is a crucial step toward bringing these therapies to the clinic. And as the first wave of ex vivo edited cell therapies enter clinical trials we will gain a greater understanding of what safety risks, if any, are posed by gene editing. This, in turn, should help to clarify the regulatory path for the subsequent wave of in vivo therapeutics.

A: How soon and how completely genome editing will reshape the future of medicine are still big questions, but I am more and more confident this will happen sooner and with a bigger impact than many appreciate. As a scientist and as a person, I could not be happier to have made this my life’s work.