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Hutch Researcher Wins "Nobel Prize of Applied Research"

R&D 100 Awards honor year's most technologically significant new products

The technological relevance of his work is being compared to the fax machine, the digital wristwatch, the automated teller machine, antilock brakes, the halogen lamp and Polacolor film.

These products are past winners of the R&D 100 Award, an international competition sponsored by "R&D Magazine" that honors the year's top 100 technologically significant new products.

This year, such recognition also will go to a gene-transfer system invented by Dusty Miller, Ph.D, a gene-therapy researcher at Fred Hutchinson Cancer Research Center in Seattle. He will receive the award -- dubbed "the Nobel Prize of applied research" and "the Oscars of invention" -- on Thursday, Sept. 24 at a black-tie banquet at Chicago's Museum of Science and Industry. Also on hand to accept the award will be research scientists from Clontech Laboratories Inc. of Palo Alto, Calif., the biotechnology firm that in 1997 licensed the patented technology from the Hutchinson Center and converted it into a marketable product.

Miller's winning technology, marketed as the Retro-X System, is a retroviral gene-transfer kit used by gene-therapy researchers at academic medical centers and biotechnology firms worldwide. It is used to introduce genetic material into cell culture and animals, specifically mammals, reptiles and birds.

In gene therapy experiments, researchers typically use viruses as vectors, or vehicles, to infect genetically defective cells with therapeutic packages of corrected DNA. The goal is to get the implanted DNA to express, or function, normally and thus cure or reverse disease.

The type of vector, or gene delivery vehicle, used in the Retro-X System is the retrovirus. Probably the most well-known type of retrovirus is the lethally efficient human immunodeficiency virus, or HIV, which causes AIDS -- obviously a potent viral messenger.

The retrovirus used in the Retro-X System is derived from a mouse leukemia virus that has been modified, or "crippled," so that after depositing its DNA cargo it can no longer replicate, or make more virus. However, it infects the host cell as if it were a normal, fully functional virus. Thus, the Retro-X System can successfully infect up to 100 percent of target cells. The system also is noted for its ability to achieve stable gene expression in those targeted cells, potentially yielding long-term therapeutic results.

While the retroviral vector in the kit is not new -- it was used in 1990 during the world's first human gene therapy trial at the National Institutes of Health -- it is the first time a retroviral gene expression kit has been made commercially available.

"It's technology that's been around for a while, but we're finally getting recognition for it," says Miller, a member of the divisions of Basic Science and Molecular Medicine at the Hutchinson Center and an affiliate professor of pathology at the University of Washington. "What's new is offering a kit you can use off the shelf," he says. The Retro-X System includes retroviral vectors, a packaging cell line to make the viruses, PCR primers -- all the components needed for retroviral gene expression. "So I guess putting it all together is what makes it exciting," Miller says.

Also attractive to researchers is the kit's new PT67 packaging cell line that is used in conjunction with a retroviral vector to create particles that can invade target cells and deliver the gene of interest. "Clontech was particularly interested in offering this packaging cell line because it was new -- this sort of mouse leukemia virus hadn't been used for packaging lines before -- and because the virus it produces can recognize two different receptors for entry into cells, unlike most other retroviruses," Miller says. As a result, the uptake is better; with two receptors, the virus is more likely to infect a variety of cells.

"These are important vectors because they not only were involved in pioneering gene therapy studies but they also allow laboratory scientists a very efficient and effective way to stably transfer specific genes -- that's really why people are buying these kits," says Steven Collins, M.D., director of the Hutchinson Center's Division of Molecular Medicine.

While an estimated 3,000 to 4,000 diseases are caused by genetic defects, the relatively new field of gene therapy has yet to provide a complete cure for any illness, although some clinical trials have looked promising. Take for example the pioneering human gene therapy trial in which two children were treated for severe combined immunodeficiency, which is caused by a defect in the adenosine deaminase gene. Today, eight years later, the immune system T cells in one of the children are still expressing a healthy copy of the gene.


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MEDIA PLEASE NOTE: A black and white photo of Dr. Miller is available upon request. However, Dr. Miller will not be available for interviews. For more information about the Retro-X System, please call Clontech Laboratories Inc. at (800) 662-CLON.

CONTACT: Kristen Woodward
(206) 667-5095

Sept. 21, 1998

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