UD News: Gene-repair pioneer, Eric Kmiec, brings his lab to the University of Delaware

September 03, 1999

Molecular biologist Eric B. Kmiec--who stunned the scientific community six years ago by inventing a technique for repairing disease-causing genetic mutations--has selected the University of Delaware as the site for his Laboratory of Gene Therapy.

Author of the landmark "350 patent" covering a specially engineered molecule that fixes "snips" (single nucleotide polymorphisms) in nature's blueprinting material, Kmiec will focus on sickle-cell anemia, Huntington's Disease and food-crop advances. He also will develop a gene therapy course while supervising graduate and undergraduate researchers at UD.

Kmiec and his half-dozen team members should play a key role in UD's rapidly expanding life sciences effort, according to Daniel D. Carson, chairperson of the Department of Biological Sciences, and Provost Mel Schiavelli.

As director of the UD Laboratory of Gene Therapy, Kmiec also is expected to work closely with the new Delaware Biotechnology Institute--a government, industry, academic partnership spearheaded by Director David S. Weir--and with researchers at the Alfred I. duPont Hospital for Children.

Why Delaware?

Kmiec (pronounced "ku-METCH") says he was impressed by UD's commitment to undergraduate education and involvement of undergraduates in research, as well as the idyllic setting.

Most convincing, however, were University faculty like Associate Prof. Cindy Carson, an internationally recognized expert in bone development who first told him about UD during a National Institutes of Health (NIH) event. The Carsons' national reputation and their ongoing study of embryonic and tumor-cell development, which Kmiec describes as "among the best anywhere," were central selling points, he adds. (Already, Kmiec plans a joint effort with the Carsons to alter certain cellular events involved in the development of breast, melanoma and prostate tumors.)

"UD chose the right people to launch a shift in their programs," Kmiec says. "I believe that this team can really make it happen for Delaware. I also appreciate the focus on undergraduates, because that's where graduate-level research begins. And, I couldn't help falling in love with the beautiful campus!"

With their two school-aged sons, Kmiec and his wife, Jennifer, the vice president of marketing at the biotech firm, Annovis, have moved to Landenberg, Pa., a few miles north of the UD campus. He previously worked for Thomas Jefferson University (TJU) and, with Jennifer, cofounded Kimeragen, the Newtown, Pa., company now gearing up for a human clinical trial of Kmiec's gene-repair technique.

"The arrival of an outstanding faculty member like Eric Kmiec demonstrates UD's efforts to become a leader in the field of biotechnology," University President David P. Roselle says. "We're pleased that Prof. Kmiec has recognized and will now be a part of the University of Delaware's growing national reputation as a center of excellence in the life sciences."

A promising synthetic "seamstress"

Kmiec credits his then-3-year-old son, Tyler, now 8, with inspiring him to develop a molecule that acts like nature's seamstress, by stitching mutated genetic sequences back together in their proper order. As Kmiec tells it, Tyler was sitting on his father's lap as they rode a tractor-mower. After hearing a lengthy description of genetic defects, Kmiec says, the boy advised him to "just put the things together."

The result, Kmiec says, was a chemically grafted or "chimeric" molecule composed of DNA and small amounts of RNA, which seeks out mismatched strands of DNA. When a genetic blooper is identified, the chimeric molecule then triggers the cell's natural repair system to replace the chemical bases in question.

In tests with human cells affected by sickle-cell anemia, Kmiec says, his gene-repair invention seems to work. Efforts to fix genetic mutations in animal models also have been promising. In the Aug. 31 Proceedings of the National Academy of Sciences, in fact, Kimeragen-sponsored researchers reported that they used Kmiec's technique on rats to correct the mutation responsible for Crigler-Najjar syndrome, which causes the toxic bile component, bilirubin, to accumulate in the body.

Kimeragen researchers, using technology licensed from Kmiec and TJU, are nearing human trials. And, other researchers worldwide are conducting promising investigations of such diseases as muscular dystrophy.

From human diseases to crop research

"Sickle-cell anemia is a terrible disease," Kmiec says of the painful group of hereditary red blood disorders caused by abnormal, sickle-shaped blood cells. "And, unfortunately, patients don't have many alternative treatment options."

His longtime collaborator, newly hired UD senior scientist Allyson Cole-Strauss, set the stage for his invention, by developing a first-of-its-kind benchtop method for studying gene repair in cells. Now, she will head the sickle-cell anemia investigation at UD. Building on previous cellular studies, she says, the team plans to examine the system's effectiveness in mice, in collaboration with duPont Hospital doctors.

Also high on Kmiec's list of priorities at UD will be studies of Huntington's Disease, to be directed by Research Associate Hetal Parekh. An incapacitating neurological disorder that causes severe memory loss and involuntary jerking movements, Huntington's usually is fatal within 10 to 20 years.

More nutritious, disease-resistant food-crops could someday result from Kmiec's invention, too, says Michael Rice, another research associate in charge of plant research. By shooting chimeric molecules into plant genes, he says, it may be possible to alter the genetic information that makes plants vulnerable to herbicides, rot and other maladies. The technique should be more precise than traditional plant-breeding techniques, Kmiec says, and less controversial than "transgenic" strategies, which involve introducing foreign DNA into plant genes.

Kmiec says he remains "cautiously optimistic" about his gene-repair technique, though he emphasizes the need for additional studies of fundamental questions. "Researchers in this field are doing excellent, promising work," he says. "But, while clinical trials are moving forward, it's important to continue to explore the mechanism of how this remarkable molecule works."

Also serving on the Kmiec research team are well-known chemist Howard Gamper, a research assistant professor at UD, who will focus on the mechanics of chimera action, and research technician Christina Johnson. She will work with Rice, completing DNA sequencing. Research by the Kmiec group will be funded by a $1 million NIH grant.

University of Delaware

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