From bench to bedside: Audrone Lapinaite sees promise in gene-editing therapies

Biochemist Audrey Lapinaite, PhD, has trained at some of the world’s most prestigious laboratories and with a Nobel laureate. The new assistant professor of ophthalmology at the UC Irvine School of Medicine aims to use that training to help develop breakthrough gene-editing treatments for patients with vision loss.

Raised in a small town in Lithuania, Lapinaite was the first in her family to go to college, studying biochemistry and earning a doctoral degree from the world-renowned European Molecular Biology Laboratory in Heidelberg, Germany. Ultimately, she came to the United States to conduct research with UC Berkeley biochemists Jamie H.D. Cate, PhD and Jennifer A. Doudna, PhD, who won the 2020 Nobel Prize in chemistry. They sparked Lapinaite’s interest in translational research.

“Working with these visionaries and pioneers, I learned not only research techniques but also the way they think, lead and interact with others,” Lapinaite says of her five years as a post-doctoral fellow at Berkeley. “They inspired what I’m doing in my own lab now, which is to first understand the molecular mechanisms of gene editing, then translate it to biomedicine and eventually use that knowledge to improve people’s lives.”

As a core researcher in the newly established Program in Precision Genome Editing, which will be housed in the Falling Leaves Foundation Medical Innovation Building, Lapinaite will be ideally positioned to bridge the gap between basic scientific research and leading-edge gene therapies. Already, she’s engaging with physicians who are treating patients at the UCI Health Gavin Herbert Eye Institute to gain insight into their needs.

“One of the things that is so exciting about being part of the Gavin Herbert Eye Institute is that it brings together scientists like me, from a basic research background, with clinicians to work jointly to address patient needs,” Lapinaite says. “To be honest, I have not seen a collaboration this strong anywhere else.”

Lapinaite’s precision gene-editing work relies on the fact that all DNA is coded with just four building blocks, known in scientific shorthand as A, G, C and T. Just a few letters off — or even one — in a lengthy series that makes up a strand of DNA can cause disease. Precision gene editing aims to use biological tools to target the exact DNA error and fix it, not unlike the “find and replace” computer function.

Advancements are coming fast. In just 12 years since the publication of Doudna’s groundbreaking research showing that CRISPR-Cas9 could edit genes, four clinical trials of precision gene-editing tools in humans are underway. Lapinaite aims to modify existing editing tools to ensure that they are safe, with the goal of advancing the science from test tubes to patient treatments. She will work closely with Krzysztof Palczewski, PhD, the Irving H. Leopold Chair in Ophthalmology and Distinguished Professor. He is developing gene-editing therapies for the eye as director of the Precision Genome Editing Program at the UC Irvine Center for Translational Vision Research.

“Recruiting Audrey is not only a personal delight, but it also strengthens our approach to genome editing, which encompasses many projects in the School of Medicine,” says Palczewski. “Audrey is also extremely precise, which is important in developing precision medicine.”

The inherited retinal diseases currently in Lapinaite’s crosshairs are Stargardt disease, a rare and inherited form of juvenile macular degeneration, and age-related macular degeneration (AMD). Editing the genes responsible for these disorders could not only treat the symptoms of blurry vision, dark spots and loss of eyesight, but also potentially prevent them in the first place.

“We are really at the forefront of developing and improving existing precision gene-editing tools to be safe enough to treat people — not in the distant future, but now,” says Lapinaite. “This is an exciting time and I am hopeful that within the next decade, we will reach the point where precision genome editing is an off-the-shelf treatment.” Lapinaite may have the opportunity to see this happen first-hand at the eye institute.

“Being a scientist, you can dream about discovering a treatment pathway that at some point might change the life of people who have a specific disease,” she says. “But here, interacting with clinicians and patients, we will have the opportunity to actually see it happen someday — and that’s the most exciting part.”

Lapinaite feels a special connection with the nearly half of UC Irvine undergraduates who are the first in their families to earn a degree. Like them, she faced many unknowns in pursuing higher education. She credits her success to both her family and the advisors who championed her along the way. Now, she hopes to pay it forward to the next generation as a faculty member dedicated to the UC Irvine School of Medicine and its mission: Discover. Teach. Heal.

“At the end of the day, future scientists, future medical doctors, future clinicians don’t just appear, they have to be nurtured,” she says. “As scientists and clinicians, this is one of the most important roles we play.”

Her advice to aspiring scientists, whether pursuing basic research or medical practice, is this: “find your supporters, people who advocate for you — who are truly invested in your success. Surround yourself with people who are ambitious, who are motivated and who try to help each other. Not everything in your career will be straightforward, but the people you meet along the way will stay in your life, and that’s what matters most.”