Scientists Find Problem & Possible Solution in Gene Therapy Delivery

Released: 11/5/2006 9:55 AM EST
Source: Dick Jones Communications

Newswise — Scientists at the University of Denver and the University of Colorado believe they are on the trail of a promising solution to a long-standing mechanical roadblock in the delivery of gene therapy.

"Gene therapy has kind of come to a halt because we can't get the DNA to the cell efficiently enough to make a difference," explains Dr. Corinne Lengsfeld, associate professor of engineering at the University of Denver.

She and Dr. Thomas Anchordoquy, associate professor of pharmaceutical biotechnology at the University of Colorado, and several graduate assistants, examined why oral nebulizers—mist generating devices that force compressed air through liquid medicine—have been such a flop at delivery of therapeutic genes.

In a series of six academic papers published within the last 18 months, the researchers explained that a process known as "cavitation" was degrading the DNA within the nebulizers themselves, thus rendering the treatment ineffective when it finally reached the lungs. The papers are listed on Dr. Lengsfeld's website: http://www.engr/clengsfe/lengsfeldpage.html.

"Cavitation is the formation of vapor or bubbles in liquid during any fluid process that puts it in tension," explains Lengsfeld. "The bubble could be stable, but if there is oscillating tension and compression it becomes unstable and collapses, creating a shock wave that annihilates the therapeutic."

Using computational fluid dynamics methods designed to describe invisible events, the research team learned that shock waves with wavelengths shorter than the DNA molecules can rip the DNA to shreds.

The DNA, however, can safely "surf" the surface of shock waves that have wavelengths longer than the DNA.

"No one in protein or DNA therapeutics had considered cavitation as a problem," notes Lengsfeld, "but cavitation occurs in every biotech processing system. We now know that if you can keep your turbulent eddy size bigger than the DNA, it will never fragment."

Thanks to a recent $500,000 NSF grant and a $75,000 grant from the Keck Foundation, Lengsfeld and Anchordoquy are building on that knowledge to develop methods to protect genes while enroute to targeted cells.

They have patented a process for encapsulating the gene with several small particles—between a tenth and a hundredth the size of the target cell. The researchers describe it as a new approach that draws on manufacturing techniques from the food processing, perfume and pharmaceutical industries. The gene capsules could be injected or delivered via aerosol.

"We're trying not to keep what we've learned secret," Lengsfeld says. "The whole reason we started this in the first place is the (pharmaceutical) companies said 'solve this problem.' Now we feel it's important to push it out there."

Anchordoquy and Lengsfeld have written a chapter on their discoveries to be published in a forthcoming pharmaceutical biotechnology handbook. And Lengsfeld has created a new fluid dynamics course at the University of Denver that incorporates their research.