Zinc Fingering Our Way to Genetic Enhancement

New York Times science reporter Nicholas Wade has fascinating article today about the development of engineered versions of zinc fingers to modify gene expression and even modify genes themselves. Zinc fingers are finger-shaped folds in certain proteins that permit them to interact with DNA and RNA. Wade describes on clinical trial in which the zinc fingers are being used to modify the immune cells of HIV patients so that they can no longer be attacked by the virus. As Wade notes:

The technique, which depends on natural agents called zinc fingers, may revive the lagging fortunes of gene therapy because it overcomes the inability to insert new genes at a chosen site. Other researchers plan to use the zinc finger technique to provide genetic treatments for diseases like bubble-boy disease, hemophilia and sickle-cell anemia.

In principle, the zinc finger approach should work on almost any site on any chromosome of any plant or animal. If so, it would provide a general method for generating new crop plants, treating many human diseases, and even making inheritable changes in human sperm or eggs, should such interventions ever be regarded as ethically justifiable….

Zinc fingers could be the gift that stem cell researchers have been waiting for. Stem cells taken from a patient may need to be genetically corrected before use, but until now there had been no way of doing so.

Dr. Rudolf Jaenisch, a stem cell expert at the Whitehead Institute in Cambridge, Mass., reported in August that he had successfully singled out three genes in induced embryonic stem cells with the help of zinc finger scissors designed by Sangamo. "This is a really important tool for human embryonic stem cells," Dr. Jaenisch said. The technology has not yet reached perfection. Some of the zinc fingers Sangamo provided "worked beautifully," he said, but some did not.

Zinc fingers may also make technically possible a morally fraught procedure that has been merely a theoretical possibility — the alteration of the human germ line, meaning the egg or sperm cells. Genetic changes made in current gene therapy are to body cells, and they would die with the individual. But changes made to the germ line would be inherited. Many ethicists and others say this is a bridge that should not be crossed, since altering the germ line, even if justifiable for medical reasons, would lower the barrier to other kinds of change.

Several scientists were reluctant to discuss the issue, or dismissed it by saying that even zinc fingers did not meet the error-free standards that would be required for germ-line engineering. But zinc finger scissors are so efficient that only 5 to 10 embryos need be treated to get one with the desired result. This could make it practical to alter the germ line.

Since the germ lines of rats and zebra fish have already been altered with zinc finger scissors, "in principle there is no reason why a similar strategy could not be used to modify the human germ line," Dr.[Matthew] Porteus, [a pediatric geneticist at the University of Texas], said. The kind of disease that might be better treated in the germ line, if ethically acceptable, is cystic fibrosis, which affects many different tissues.

The disease could be corrected in unfertilized eggs, using the zinc finger technique, Dr. Porteus said. But he added, "I don't think our society is ready for someone to propose this."

Who's not ready? In any case, see the whole Wade article here.