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Zinc Fingers Bear Fruit

A method for precise gene editing is able to change disease-causing point mutations in human stem cell DNA.

Jul 18, 2011
Bob Grant

Zinc finger proteins (blue) bound to DNA (orange)THOMAS SPLETTSTOESSER, WIKIMEDIA COMMONS

Researchers have, for the first time, modified a single, disease-causing mutation without altering any other parts of the genome in human stem cells. Scientists in Rudolph Jaenisch’s lab at the Whitehead Institute for Biomedical Research used zinc finger nucleases (ZFNs) to carefully insert or remove a single base pair in the alpha-synuclein gene—which is known to play a role in Parkinson's disease (PD)—in induced pluripotent stem (iPS) cells. Such precise and targeted genetic manipulation could help avoid problems associated with messier methods of gene alteration, such as virus-mediated editing, that complicate the use of stem cells as therapeutic agents. "ZFNs can transfer a mutation without any other alterations to the genome, such as leaving in unwanted pieces of DNA that could be harmful," postdoc Frank Soldner, first author on the paper, published last Thursday in Cell, said in a statement. "This precision is ideal for drug research for PD and other diseases, but it is also one more step toward using ES or iPS cells therapeutically."

Earlier this month, two other postdocs in Jaenisch's lab used transcription activator like effector nucleases (TALENs), which have gene editing powers similar to those of ZFNs, to precisely and efficiently edit genes in both human embryonic stem cells and iPS cells. That work was published in Nature Biotechnology.

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