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Zinc Fingers

With zinc finger technology, scientists might be able to “cut and paste” DNA to fight certain diseases.

SPRING 2010
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zinc fingers [ziŋk 'fiŋgərz] n: proteins found naturally in plant and animal cells that might yield an improved form of gene therapy and are the focus of current attempts to treat HIV/AIDS by mimicking a mutation that makes people resistant to the virus.

Zinc fingers—so-called because each molecular “finger” has a stabilizing zinc atom at its center and because researchers, first seeing them in 2-D, thought they looked like fingers (in fact, they’re U-shaped)—naturally regulate the activity of genes by binding to DNA. Cambridge University chemist Aaron Klug, who discovered the proteins in 1985, and others have spent the past 25 years trying to create customized zinc fingers that can edit human DNA by knocking out or adding gene sequences, adding beneficial mutations or correcting disease-causing ones.

The University of Pennsylvania and Sangamo BioSciences are using customized zinc fingers—known as zinc finger nucleases (ZFNs)—in attempts to simulate one particular, beneficial mutation: the disruption of a gene called CCR5 from human DNA. Because CCR5 is essential for common types of HIV to enter immune cells, people born without a functional CCR5 gene are resistant to HIV infection. Researchers are using ZFNs to disrupt the gene from HIV patients’ DNA in hopes that once a CD4 T-cell (the most important white blood cell for fighting HIV/AIDS) does not make functional CCR5, HIV/AIDS will be unable to kill that cell, decreasing the patient’s viral load and improving his or her immune system.

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