University of Hawaiʻi at Mānoa researcher Jesse Owens has received a $2 million NIH (National Institutes of Health) grant to advance his lab’s pioneering gene-editing technology at the John A. Burns School of Medicine (JABSOM).
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“This is my dream grant,” said Owens, associate professor at JABSOM’s Department of Cell and Molecular Biology. “It’s the project I’ve always wanted to do. It funds exactly what our lab is passionate about, which is developing safer, more precise tools for gene therapy that can be used across many different diseases.”
The four-year, $2 million R01 award supports Owens’ effort to create a new generation of transposases, the specialized enzymes that insert genes into precise genome locations. Unlike other gene-editing tools such as CRISPR—which cut DNA and can sometimes lead to unwanted mutations during the repair process—Owens’ method replaces genes without cutting or exposing the DNA, allowing for safer and more precise gene delivery.
Refining precision in gene therapy
That precision is the result of years of meticulous research. Graduate student Chris Tran created and tested more than 200 mutated enzymes to find one that makes very few mistakes and changes only the intended genes without affecting others. The lab’s next goal is to improve the system’s “on-target” efficiency—the rate at which genes land exactly where intended.
“Our goal now is to find that perfect balance,” Owens said. “We’ve minimized the off-target effects; now we’re working on boosting the on-target performance so that the system is both incredibly safe and incredibly effective.”
Owens’ lab has already made remarkable progress. Early versions achieved less than 1% gene delivery efficiency. Through years of refinement, the latest system now reaches nearly 100% efficiency, a leap Owens once thought impossible.
“What we didn’t realize early on was just how fine-tuned this system needed to be,” he said. “If you move the target by just two base pairs, the efficiency can drop dramatically. We had to test hundreds of iterations to find the right combination.”
Building tools to fight many diseases
Owens describes his lab as “disease agnostic,” building tools that can be applied broadly, from hemophilia to cystic fibrosis to cancer.
Imagine something that started in your PhD eventually becoming part of a therapy that fights cancer.
—Jesse Owens
“It’s a special type of R01 (grant),” he explained. “It’s not tied to one disease area, which is perfect for us. We can focus on making the best tool possible, and then share it with researchers who specialize in different diseases.”
Ultimately, Owens hopes the technology will accelerate CAR T immunotherapy, which reprograms immune cells to destroy cancer. His team plans to test the system in human T-cells before collaborating with clinical researchers.
“The really exciting thing is that this could one day help treat actual patients,” Owens said. “Imagine something that started in your PhD eventually becoming part of a therapy that fights cancer. That’s what drives us.”
The grant also supports two JABSOM graduate students, providing hands-on experience at the forefront of gene therapy research.
“Dr. Owens and his team are not only advancing the science of gene editing, they’re inspiring the next generation of scientists who will continue our legacy of innovation and discovery,” said JABSOM Dean Sam Shomaker.
