Wash That Gray Right Out of Your Hair THE REVIVAL OF GENE THERAPY
By Meredith Wadman

(FORTUNE Magazine) – A breakthrough by a group of researchers in Philadelphia may help reinvigorate the struggling field of gene therapy and portend a future in which Just For Men hair color is history.

Scientists at Jefferson Medical College reported in the January issue of Nature Biotechnology that they have turned hair dark in albino mice using chimeraplasty, a type of gene therapy that repairs faulty genes rather than replacing them. The work boosts enthusiasts who hope that gene therapy will eventually treat everything from grayness to balding. It was also happy news for Kimeragen, a small private company with just 37 employees in Newtown, Pa., that holds an exclusive license on chimeraplasty. The experiment "is one more step forward [showing] that the technology is robust," exults Lisa Malseed, vice president for strategic planning and licensing.

Chimeraplasty differs from standard gene therapy, in which scientists use disabled viruses to deliver whole new genes intended to function in place of defective ones. Standard gene therapy is hampered by imprecision. A gene may insert itself anywhere in the genome, which can throw off its regulation: The gene might "turn on" at the wrong time or make abnormal amounts of the protein whose production it directs. Another danger is that the viruses that act as limousines for the inserted genes can cause the immune system to go into overdrive in an attempt to eliminate what it perceives as foreign invaders. Researchers think that this is a big part of what killed Jesse Gelsinger, an 18-year-old research volunteer at the University of Pennsylvania who died in September while undergoing gene therapy to treat a rare metabolic disease.

Chimeraplasty doesn't rely on viruses for delivery. Instead of inserting new genes haphazardly, it repairs faulty genes with surgical precision, using molecular messengers to correct misspellings in the genetic alphabet. For instance, in the case of the albino mice, the misspelling blocked an enzyme that's crucial for the production of the pigment melanin, which gives hair its color. The repair tools were actually DNA-RNA pieces, dubbed chimeras, which contained the correct spelling. They repaired the faulty gene with surgical precision by harnessing the cell's own DNA repair mechanism. The upshot: In the albino mice, the genetic imprecision was reversed, and the mice began sprouting dark hair.

Don't rush to your doctor for restoration of your lustrous locks just yet. "We were able to generate only a few black hairs, detectable only under the microscope," notes lead researcher Kyonggeun Yoon, a chemist and molecular biologist at Jefferson. And the change in the mouse hair color lasted just three months because of the short life span of the pigment-producing cells. To spur permanent change, scientists will need to find a way to repair genes in the precursor cells that give rise to all pigment-making cells.

Still, some argue that gene therapy will yield a future of 80-year-old full-headed blonds. "Gene therapy has just taken a cosmetic step forward," wrote Robert Hoffman in a commentary accompanying Yoon's report. Hoffman is president of AntiCancer, a privately held biotechnology company in San Diego that is a pioneer in hair gene therapy. Hoffman's firm is targeting ordinary graying, which is caused by the natural deterioration of pigment-producing cells that comes with aging, not by genetic misspelling. AntiCancer hopes to stimulate pigment production by inserting extra copies of the gene that Yoon repaired or by inserting the gene into other kinds of hair cells and hijacking them to do the job.

But Yoon herself--who launched her experiment with the ultimate goal of treating not graying heads but disfiguring skin diseases--cautions that widespread commercial applications are "more than premature." "The technology is not ready for that kind of venture," she says.

--Meredith Wadman