Ralph Shohet

Researchers at the Center for Cardiovascular Research at the University of Hawaiʻi John A. Burns School of Medicine (JABSOM) hope that patients with hemophilia could one day be treated with gene therapy delivered by tiny bubbles.

The microbubbles are made of lipid molecules that won’t dissolve in water. The bubbles are made with DNA that expresses therapeutic genes, and are then injected into the bloodstream. As the bubbles pass through the liver, a beam of ultrasound pops them, and the DNA is deposited in the liver cells, where it makes the missing clotting factor. Hemophilia is an attractive target for gene replacement therapy because the disease results from a single gene mutation, and low levels of the normal protein can restore clotting function.

“Hemophilia is a chronic debilitating disease. If we can treat it simply, cheaply and noninvasively with gene therapy we will have helped to fulfill the promise of the modern medical era,” said Professor and center Director Ralph Shohet.

The technique could provide an alternative to current treatments for hemophilia, which require frequent injections of a protein (Factor VIII or Factor IX), which is expensive and inconvenient.

“We were able to improve clotting in mice for months after a single treatment,” said Shohet.

Hemophilia affects about 20,000 men and boys in the United States and perhaps 400,000 worldwide. Most affected individuals have a severe form of the disease and suffer from frequent and spontaneous bleeding episodes that can result in serious complications.

The study was led by JABSOM researchers Cindy Anderson and Chad Walton. Other investigators included JABSOM’s Abigail Avelar and Stefan Moisyadi of the Institute for Biogenesis Research.

The findings were published in the scientific journal Gene Therapy.

—By Tina Shelton

As the microbubbles flow through the blood vessel they are disrupted by ultrasound, leaving their ‘payload’ of gene constructs in the organ of interest. Right, the camera detects a light-producing protein that was delivered to the mouse’s liver using ultrasound directed microbubbles.