Researchers Erik Aznauryan and Tina Lebar are working together to overcome the limitations of gene therapies that have existed for decades with their HarborSite technology
By Jessica Leff
On October 15, 2019, two researchers joined the lab of Core Faculty member George Church, Ph.D., at the Wyss Institute. One, Tina Lebar, Ph.D., came from Slovenia to begin a postdoctoral fellowship. The other, Erik Aznauryan, Ph.D., was a visiting Ph.D. student studying in Switzerland. The two got to know each other as they went through lab tours, safety training, and other orientations together. Aznauryan soon joined a journal club, where they reviewed one of Lebar’s papers from her previous lab. They ended up sitting near each other, and formed a friendship, though they were not working on the same project.
In July 2021, Aznauryan returned to the Wyss after earning his Ph.D. He was split between two projects – one that continued his work as a visiting student, and another with Lebar. Eventually, they both decided to focus their efforts on their promising platform technology, which was called HarborSite.
A genome editing innovation to treat diseases
HarborSite is a genome editing technology that allows for precise insertion of large DNA sequences into specific spots in the genome for safe, lifelong expression of therapeutic genes.
It has three major benefits over other genome editing tools. First, HarborSite addresses multiple mutations at once by precisely inserting whole genes into the genome. Durability is another key feature – the therapeutic effect doesn’t wane over time following targeted insertion. Finally, the fact that therapeutic genes are inserted at a specific place in the genome where they are unlikely to interact with other genes makes it safer than existing methods.
We do such advanced work in the lab, but when we go to our doctors they still mostly prescribe drugs and tests from decades ago. Being able to progress that, even a little bit, is super exciting.
Because this is a platform technology, it can be applied to a variety of applications. The team is currently focusing on diseases that can be treated by gene insertion into liver cells, such as hemophilia.
Two primary components, two complementary team members
HarborSite consists of two proprietary genome editing technologies – and the team consists of two researchers uniquely suited to develop them. One component is the enzyme that makes the insertion. Lebar began her studies in mammalian synthetic biology, and over time transitioned to specializing in protein engineering, making her a great fit to refine the enzyme. The other aspect is finding the spots to make the insertions safely. Aznauryan’s history in genome editing allows him to discover these locations and evaluate how efficient and safe the insertions are in different cell types.
Aside from their technical expertise, their personalities and interests make them a great team. Aznauryan is more extroverted. While he loves research, he’s also interested in entrepreneurship. So, he’s comfortable taking the spotlight and leading those efforts, planning to stay with the technology once it leaves the Wyss. Lebar is more introverted and focused on the academic developments behind the technology. She looks forward to one day having her own lab and continuing to develop this work while staying connected to the company.
The two know that having different strengths that complement each other is part of what makes them a great team. Aznauryan jokes, “Plus, I’m really tall, so if she needs to reach something in the lab, I can get it for her.”
The other secrets to their successful partnership are communication and compromise. Lebar explains, “We try to talk about things openly and if there are problems, we solve them as soon as they arise, so they don’t pile up.” Aznauryan adds, “We’ve managed to align our focuses in academic research and company development so that everyone’s interests are maintained.”
Solving a decades-old mystery
Since that day in 2019, HarborSite and the researchers working on it have come a long way. Both scientists transitioned from juggling multiple projects to solely focusing on this one. Lebar explains, “When I was a kid, I was interested in doing crossword puzzles and solving mysteries – I’d read all of the Agatha Christie novels by the time I was twelve. To me, that’s what this project is. It’s solving a problem that’s been around for about 20 years. It’s figuring out a puzzle while trying to make a difference, because I know the mystery I’m solving will be useful for genome editing and eventually therapeutics.”
To me, that’s what this project is. It’s solving a problem that’s been around for about 20 years. It’s figuring out a puzzle while trying to make a difference, because I know the mystery I’m solving will be useful for genome editing and eventually therapeutics.
Aznauryan adds, “It’s really cool to see something that you’ve been working on in the lab for so long ultimately become something useful in medicine. We do such advanced work in the lab, but when we go to our doctors they still mostly prescribe drugs and tests from decades ago. Being able to progress that, even a little bit, is super exciting.”
Both Lebar and Aznauryan are motivated by the translational potential of the technology, and the possibility of having an impact. They see HarborSite’s potential use in making new medicines for challenging conditions and are enthusiastic about using the knowledge they’ve acquired to help patients.
HarborSite was chosen as a 2022-2023 Validation Project and renewed for 2023-2024, which has allowed for further de-risking and refining of the technology. Validation projects receive dedicated funding, business development support, and additional resources. Aznauryan explains, “I don’t know of many other institutions that have this internal funding structure available to support so many projects at the early stages, and that’s amazing, but it’s not just the money. It’s also the people surrounding you. An interesting connection happens immediately between the researchers working on Validation Projects aiming to translate their work, which leads to a lot of collaboration and support.” Business Development Manager, Bill Bedell, Ph.D., works with the team, and Church and Jenny Tam, Ph.D., Director of Synthetic Biology, provide mentorship and guidance.
Lebar adds, “The Wyss is a unique environment that’s very translation orientated. It’s like nothing I’ve ever seen or heard about before, and it’s wonderful.”
Both Aznauryan and Lebar are eager to see this project continue to advance and eventually reach the clinic. As they further refine and de-risk their technology with the goal of eventually forming a startup, they’re looking for investors and industry collaborators to help them realize their vision.