Zinc fingers and gene therapy
There’s a new treatment for a few genetic diseases on the way. In a paper published in the June edition of Nature, Nobel laureate and president of CalTech, David Baltimore and Mathew Porteus of Sangamo BioSciences outlined a new approach to curing severe combined immunodeficiency disease (SCID, commonly known as “bubble-boy syndrome”) using zinc fingers to slice out defective portions of patients’ genes.
Specifically, the technique involves utilizing a built in cell DNA repair function called homologous recombination. Basically, cells have a built-in ability to repair DNA strands that have been cut using a sort of “master” DNA template. So if researchers snip out the defective part of the DNA, the strand is repaired using homologous recombination and a donor DNA template.
The technique is similar to a previous 2002 attempt to cure SCID, in which twelve patients were delivered a foreign gene using a retrovirus as the vector. Unfortunately, three of them developed leukemia and died, but the other nine were cured. The problem with that attempt was that sometimes the protein coded by the foreign gene not only vanquished the SCID gene, but also sometimes turned on a cancer-causing gene, because of the lack of specificity.
However the new approach doesn’t have this problem. The previous French attempt introduced the new gene randomly into the patient’s body. Zinc fingers, on the other hand, can only land at very highly-targetted spots on the patient’s DNA, and as such, they do not carry the risk of turning on cancer-causing genes.
“They’ve certainly raised the bar for gene-therapy safety,” said Scott Wolfe, a zinc-finger researcher at the University of Massachusetts Medical School in Worcester, Massachusetts. He points out that the early proof-of-principle work was highly toxic to the cells. The zinc fingers weren’t specific enough and they created so many double-stranded breaks in the DNA that a lot of the cells chose to commit suicide rather than try to repair all the breaks. “They really seem to have solved the toxicity problem altogether.”
The technique also shows promise for some types of cancer patients, AIDS patients, and even those with cystic fibrosis. Eventually if the approach is successful, zinc finger gene therapy could be used to target almost any genetic disease, with the only limitation being how much one could customize a zinc finger.
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This was very breif yet informative article. Thank you very much.
Comment by Rachel — January 26, 2006 @ 10:36 am