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Hair Gene Therapy
January 13, 2000

Imagine going into a hair salon and asking for a wash, cut, and gene therapy to get rid of your gray hair. Although this may be far off in the future, researchers have shown for the first time that they can change the color of an animal’s hair through a new type of gene therapy. But the possibilities go far beyond a high-tech dye job. The new technology could lead to safer and better gene therapy techniques for treating serious human diseases, too.

In Living Color

Researchers at Jefferson Medical College in Philadelphia have used the new technique, called chimeraplasty, to make albino mice grow black hairs. Although they were able to correct a mutation in tissue cultures of albino mouse cells last year, this is the first time they have been able to obtain the same results in living animals.

"I think that this is a considerably new approach of doing gene therapy—that we are trying to correct the mutation. . . rather than supplying the entire gene," says Dr. Kyonggeun Yoon, associate professor of dermatology and cutaneous biology, who participated in the research, which was reported in the journal Nature Biotechnology (Vol. 18, January 2000).

Yoon and her colleagues were able to achieve this by chemically synthesizing a small piece of genetic material—called an oligonucleotide—containing both DNA, with the corrected pigment-producing gene, and RNA, which seems to stimulate the matching of genetic sequences. This then acts as a blueprint that tells the mouse’s own gene repair mechanism how to fix the mutation.

Microscopic view of a few black hair

The RNA-DNA nucleotide was then repeatedly applied to the skin of the mice, as well as injected. Within two to three months, researchers observed black hairs. Although the number of colored hairs is so few they have to be seen under a microscope, researchers analyzed the mouse DNA and found that it had corrected the albino mutation. The effect lasted up to six months, in spite of the fact that hair grows out and is continuously renewed. Yoon said she believes the team was able to reach at least some epidermal stem cells—which give rise to other skin cells, such as pigment-producing ones—because the pigmentation lasted more than one hair cycle.

What The Future Holds

Unlike other gene altering techniques, chimeraplasty doesn’t use a virus to carry the new gene into the body. Using viruses presents some risk, since they can provoke an immune reaction. So this technique may prove to be a safer form of treatment, according to Yoon.

Epidermolysis bullosa.
image: DebRA

But what conditions it should be used to treat is a controversial topic. Yoon says there has been too much hype about using the technique for cosmetic conditions, such as gray hair or hair loss. She cautions against using gene therapy when it’s not necessary and points out that the technique still has quite a way to go in terms of effectiveness. Her hope is that it will eventually be used to treat life-threatening skin cancers and painful, disfiguring skin-blistering diseases like epidermolysis bullosa.

"For dermatological applications, if we can improve the efficacy of this and. . . if it can help some people with serious diseases where there is no current cure, I think that’s quite worthwhile to do it," she says.

It may be that hair follicles act as a kind of doorway in the skin. According to Yoon, in hairy animals at least, the hair provides some sort of open avenue that allows small molecules to penetrate deep into the dermis.

Other research seems to support this. In September, researchers testing a DNA vaccine reported in the journal Nature Biotechnology that the vaccine worked if it was dripped onto skin, as long as the skin had hair on it.

Hoffman has even suggested that because hair follicles have a high capacity for manufacturing proteins, they could be used for other purposes. "Why not take over the hair follicle to make medically useful products, instead of hair," he said. "Why not subvert the process and make them factories?"

It’s also not clear whether the technique would even work for cosmetic corrections, because scientists don’t know if these problems are caused by genetic alteration. "It’s not clear whether cells that produce pigment are lost or lose function," said Dr. Robert Hoffman, president of AntiCancer, Inc., a biotechnology company that develops cancer treatments. Even if cells lose function, however, Hoffman says scientists could try to augment the genes as opposed to repairing them, as Yoon has done. "If the cells themselves die out, perhaps we can transfer their capabilities," he said. "I think in science we should never close the door on possibilities."

Right now, the Jefferson team has only been able to affect a small percentage of pigment producing cells with chimeraplasty. So until scientist figure out how to repair more of the problematic cells, you won’t be seeing this therapy at the doctor’s office, let alone the local salon.

Elsewhere on the Web

The American Society of Gene Therapy

Information about treating skin diseases

Find a dermatologist

The American Academy of Dermatology

by STN2

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