From Yeast to Humans: A Researcher’s Journey in Gene Editing and Therapeutic Innovation

Prof. Adi Barzel’s journey from academic discovery to biotech entrepreneurship, building breakthrough gene therapies for HIV, cancer, and beyond

Written by Orry Baum

In the early days of his scientific career, Prof. Adi Barzel was interested in one of biology’s most fundamental questions: how do cells repair broken DNA? “At the time, as a PhD student in Martin Kupiec’s lab, we were interested in DNA repair, asking the question: How do cells repair broken DNA? In order to study that basic question, we used enzymes that could cleave the DNA at the desired location, after which we followed the repair processes.”

That curiosity, shared by many at the time, laid the groundwork for what would become a lifelong pursuit. “I had the thought, as did many at the time, some twenty-something years ago, that if such enzymes are available, which can cleave the genome at a particular location, then perhaps we can find use for them in gene therapy, what later became known as genome editing.” That path led him to Stanford University and eventually to methods for correcting genetic disorders directly in the liver. “We found ways to ameliorate these deficiencies by providing the required gene to the hepatocytes, the cells of the liver.”.

Engineering immune cells inside the patient's body

The Science Behind the Startup: Precision, Safety, and Genomic Hitchhiking

One of the key advances developed during his Stanford postdoc was a technique for safer, more targeted gene delivery. “We were able to deliver a desired gene that the child is missing into the liver cells of that child, without requiring a nucleate. It was still site-specific, but what determined the site-specificity was strictly the design of the vector with the appropriate sequences called homology arms, and that was much safer than previous technologies.”

The innovation went further with what he describes as a promoter-less strategy. “Our vectors did not contain a sequence that drives expression. Only upon on-target integration was expression possible, and that was made possible by hitchhiking on an endogenous promoter.” He elaborates: “We went into a place in the genome where expression is already very high and we hitchhiked. We took advantage of that high expression of the endogenous locus and conferred that to our engineered integrated gene.”

This method proved especially powerful in conditions like Hemophilia B. “The coagulation factor is expressed if and only if it is integrated into the desired location, the desired location being the albumin locus in the liver. Even rare integration events could lead to high expression of our coagulation factor, because these rare engineered cells act as factories.”

Prof. Adi Barzel

Translating Discovery Into Impact

Barzel’s academic insights led to real-world ventures. “The first related to the liver gene therapy, that was a spin-off of Stanford. It became a public company, LogicBio Therapeutics, and was later sold to AstraZeneca.” That journey from postdoc to public company would later inspire two more ventures out of his lab at Tel Aviv University.

“So our lab was among several pioneering labs in the field of B cell engineering,” he says of Tabby Therapeutics, which targets HIV by engineering B cells to express protective antibodies. “Later development allowed us to perform this engineering inside the body. You take a vial out of the freezer and you inject the vector, all this to be done in vivo.” A third company, Zelig Therapeutics, builds on CAR-T technologies to eliminate IgE-producing cells, offering a potential cure for severe allergies: “If it was possible to find all the cells that produce IgE and kill them, so we will do well without IgE.”

Reflecting on the transition from academic lab to startup founder, he describes a steep but rewarding learning curve. “To move out of academia and start knocking on doors of venture capitalists was quite a thrill. It’s lots of work but lots of fun and it's exciting to see the technologies mature from a starting from the whiteboard behind me and moving to the tissue culture and to mice and then later into companies and into clinical trials in humans.”

Prof. Barzel is also acutely aware of the challenges facing biotech entrepreneurs in Israel: “The major challenge in our field is the C-level team. We are not a mature ecosystem in Israel. We don't have many people with the required experience to lead such companies. So when we're trying to tackle this, for example, my current company uses many Israelis that live abroad and have experience in the US.”

Ultimately, for him, science is not just a pursuit of knowledge, it's a mission. “I don't want to be a poet that writes songs and puts them in a drawer. It's all for the benefit of the public. I find that it enriches and makes better my academic research that I also engage in translation and in the clinic.”

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