NYT:
September 14, 2004
Another Approach: Fingers on the Genetic Switchboard
By ANDREW POLLACK
NA interference is not the only new way to control the activity of genes in the body. When 81-year-old Peter Cummins received 10 injections in each of his legs last month, he became part of the first human testing of another potentially promising method: proteins known as zinc-finger transcription factors.
The proteins, which are vaguely finger-shaped, are found naturally in the body, where they turn genes on and off by wrapping around DNA in the chromosomes. Scientists are learning how to make zinc fingers that can attach to any particular DNA sequence.
"It's kind of like the guidance system of a missile," said Edward Lanphier, chief executive of Sangamo BioSciences of Richmond, Calif., which developed the drug being tested in the trial.
Mr. Cummins, a retired Navy pilot who lives in Falls Church, Va., has blockages in his leg arteries that cause severe pain during physical activity. He must use a cart during his frequent golf outings. The drug injected into his leg - assuming he did not receive the placebo that some patients in the trial are receiving - is intended to turn on the gene for a protein that would spur new blood vessels to grow in his legs.
Zinc fingers are potentially more versatile than RNA interference because they can turn genes either on or off, while RNAi works only as an off switch. The fingers might one day even help repair mutations in genes.
Still, RNAi has generated much more excitement because it is easy to use and has been widely adopted by scientists. Zinc fingers are much more difficult to make. While numerous companies are pursuing RNAi, Sangamo has a virtual monopoly on zinc fingers because it has licensed most of the early patents from the academic pioneers of the field.
The biggest obstacle to use of the fingers is expected to be delivery into the body. The zinc-finger proteins themselves are hard to get into cells and probably would not last long. So Sangamo's drugs consist of genes to allow a patient's cells to produce their own zinc fingers - although effectively inserting genes into people has been notoriously difficult.
The trial involving Mr. Cummins will enroll 36 patients and take up to two years, according to Edwards Lifesciences of Irvine, Calif., which has the rights to market the drug. If the early results are promising, larger trials taking several more years are likely to be needed before the drug can reach the market.
"I'm hopeful it will work," Mr. Cummins said. "If it doesn't, it doesn't."
And if it does? "I'd like to walk the golf course again." |
