Above: Assistant Professor Jesse Owens using a program to model the structure of his integrase protein Credit: JABSOM
WHAT IF, INSTEAD OF TRYING TO FIX DIFFERENT GENE MUTATIONS for different people, one could simply replace the entire mutated gene, safely, efficiently, and precisely?
In one of the most genetically diverse states in the nation, University of Hawai‘i at Mānoa John A. Burns School of Medicine (JABSOM) Assistant Professor Jesse B. Owens is turning this radical idea into a therapeutic reality. Owens and his team are developing a new gene delivery platform that could revolutionize how doctors treat everything from rare blood disorders to aggressive cancers.
“I want to replace the entire gene, no matter where the mutation is — use one therapy for everyone,” said Owens. “For example, if the gene were a car and one person had a flat tire, and another person had a broken windshield; instead of going to two different shops to do two different repairs, each person just got a brand-new car right away, for no more than the cost of the repair. This could lead to faster, more affordable treatments for a wide range of diseases.”
What Is Gene Therapy?
The thousands of genes that determine various traits and characteristics of humans, including looks, personality, and body functions — stem from the long, twisted, step-ladder of molecules known as deoxyribonucleic acid (DNA). Each step, or base, makes up the body’s genetic code, an instruction manual that dictates how cells build and function. Changes to, or mutations in one’s genes can cause genetic disorders like hemophilia, cystic fibrosis, sickle cell disease and even certain types of cancer.
For decades, researchers have been developing and advancing gene therapies to fix, replace or even switch faulty genes in order to treat and prevent diseases. Most approaches use engineered viruses or editing tools to deliver the corrective DNA into a patient’s cells.
One of the most widely used gene therapies today is known as Clustered Regularly Interspaced Palindromic Repeats or CRISPR, co-developed by Hilo, Hawai‘i native Jennifer Doudna, who earned the Nobel Prize in Chemistry in 2020. CRISPR works like a pair of scissors, cutting DNA at specific locations, then harnessing the cell’s repair system in hopes that it figures out how to modify or insert the new gene.
Despite its ubiquitous application, however, CRISPR has its limitations. It struggles to insert large pieces of DNA required to replace whole genes for curing diseases like hemophilia and cystic fibrosis, which are caused by a single gene defect. The CRISPR procedure can also be risky. By causing double-stranded breaks in the genome, where both strands of the DNA double helix are severed, unwanted mutations and further genetic disorders, including cancer, are possible. Also, while CRISPR excels in dividing cells like those found in labs, it is far less effective in the non-dividing cells that comprise the majority of the adult human body.
From Cutting to Inserting: A Paradigm Shift
Owens’ technology represents a dramatic departure from the CRISPR paradigm. Rather than cutting DNA and relying on the cell to make repairs, his method acts like biological glue — actively inserting large, healthy genes directly into the genome that then take over for the defective gene.
The key is a family of viral enzymes called integrases, which facilitate the insertion of DNA into host genomes. Owens’ lab uses a controlled process called “laboratory evolution” to engineer “super-active” enzymes, dramatically boosting their precision and efficiency for inserting genes of interest.
“With these specially engineered integrases, we’re able to carefully insert healthy genes into an exact location without causing breaks in the DNA,” said Owens. “This insertion function has very high efficiencies of up to 96 percent in human cells, which is unprecedented.”
Treating Hemophilia and More
One of the early goals of Owens’ lab was to demonstrate efficient large gene insertion precisely into the human genome. This technique, if successful, could be well suited to treat genetic bleeding disorders such as hemophilia and von Willebrand Disease. Rather than fixing each mutation in the gene individually, as CRISPR might attempt, Owens’ approach would simply install a new, functional version of the gene. To help prove this concept, Owens’ team recently demonstrated the successful insertion of the large von Willebrand factor (VWF) gene into human cells. As one of the largest genes associated with bleeding disorders, the VWF gene provides the body with instructions for making the von Willebrand factor, a protein crucial for blood clotting. This success has paved the way for the potential use of this technology to treat neurological disorders, immune deficiencies, and even cancers, by inserting therapeutic genes into non-dividing cells — something CRISPR has long struggled with.
“Our results show that we can precisely deliver a correct version of a large gene while maintaining high efficiency of DNA integration,” said Owens. “This approach opens the door to possible development of therapeutic options for previously untreatable genetic diseases.”
Local Roots, Global Impact
Owens was raised in Hilo like Doudna, the co-developer of CRISPR. His scientific drive emerged early: “Back when I was 17, I had to figure out what my goal was going to be,” he recalled. “I really liked the idea of delivering DNA into the genome of animals or people and how moving DNA around could treat diseases.”
After graduating from Hilo High School, Owens earned his undergraduate degree in molecular, cell and developmental biology at the University of California Santa Cruz. He then returned to Hawai‘i for graduate studies at
JABSOM, where he began working with Associate Professor Stefan Moisyadi at the Yanagimachi Institute for Biogenesis Research on jumping genes, or transposons — mobile genetic elements that laid the groundwork for today’s integrase-based genome engineering platform.
Commercializing His Research
In 2024, Owens helped launched KOMO Biosciences (KOMO), a precision genome engineering technology startup spun out of the University of Hawai‘i (UH) which focused on addressing urgent unmet genome engineering challenges. KOMO is now commercializing Owens’ integrase technology platform with multiple applications in biomanufacturing, cell and gene therapy, agriculture, and synthetic biology.
In biomanufacturing, for example, the integrase platform can accelerate the engineering of cell lines that produce therapeutic proteins, such as antibodies, by efficiently inserting large fragments of DNA at specific sequences in cells. “What used to take months, we can now do in in a few weeks,” Owens noted — something that could dramatically speed up responses to emerging health threats like pandemics.
KOMO is currently working to collaborate with manufacturers of biological therapies to accelerate timelines and reduce the cost of cell line development for antibodies and proteins. The company is also collaborating with organizations to develop safer and more reliable chimeric antigen receptor T-cell (CAR T-cell) therapies, which involve equipping a patient’s immune cells with genes to enable them to recognize and destroy cancer. Current methods focus on inserting these genes randomly into the genome, while Owens’ approach targets them to specific “safe harbor” sites, reducing the risk of harmful side effects.
“CAR-T immunotherapy is probably the best anti-cancer therapy out there right now, but we think we can make it better,” said Owens.
The Future of Gene Therapy
Though there is still a long path ahead — from animal models to clinical trials — Owens’ technology may represent one of the most significant advances in gene therapy since CRISPR. Backed by National Institutes for Health funding and protected under UH patents, Owens’ technology has the potential to transform the treatment of diseases caused by single-gene defects — impacting hundreds of conditions with a single, highly efficient tool. Additionally, his integrase-based platform technology could transform how these therapeutics are manufactured while reducing their production costs, ultimately leading to faster and more reasonable treatments, and saving millions of lives.
Owens has also launched a non-profit called Hawai‘i Advanced Genetic Medicine Foundation, which will eventually support grants to advance genome editing and genetic medicine research in Hawai‘i.
“Our lab is focused on overcoming some of the most difficult challenges in genome engineering,” said Owens. “The goal is to build the tools that will make tomorrow’s medicine possible.”