To find a new, gentler approach to developing tolerance, Herzog teamed with Henry Daniell, Ph.D., a Pegasus professor and University Board of Trustees Chair in the College of Medicine at the University of Central Florida, who has spent the last two decades developing transgenic plants for producing and delivering oral vaccines and immune-tolerant therapies.

They inserted the gene responsible for producing the therapeutic protein into the genome of plants. To maximize the amount of protein produced, they inserted thousands of copies of the genes into chloroplasts - the energy-producing centers of plants - using a gene gun.

The research team, including first authors Dheeraj Verma, Ph.D., and Babak Moghimi, M.D., fed the encapsulated protein to hemophilic mice for an extended period. Surrounded by the hardy plant cell walls, the protein was protected from digestive acids and enzymes while traveling through the stomach. Once it arrived safely in the small intestines, however, surrounding bacteria chewed on the cell walls, causing the protein to be released and acted on by the immune system to induce tolerance.

When the mice were later treated intravenously with the clotting factor therapy, they produced little or no inhibitors, and none developed anaphylactic shock.

"We have made them develop tolerance, and removed the allergic part of this treatment," Daniell said.

Not only did the pretreated mice survive the once-deadly treatment - they also had a greater positive effect from therapy than did other mice.

"You may wonder, 'why hasn't this happened before,'" Vandendriessche said. "It's because it was difficult to administer a high amount of protein in the right place and at the right time. I think this is a milestone - nobody has previously achieved such levels of robust immune tolerance by any means using a noninvasive procedure."

The researchers will continue to study how their method works, extend the approach to treating hemophilia A in mice and, ultimately, conduct trials in humans. Protein used in the human trials will be produced in lettuce and formulated to allow delivery of standard doses.

Source: University of Florida