Gene targeting technique extended to human embryonic stem cells

MADISON - The technique that helped revolutionize modern biology by making the mouse a crucible of genetic manipulation and a window to human disease has been extended to human embryonic stem (ES) cells.

In a study published today (Feb. 10) in the online editions of the journal Nature Biotechnology, a team of scientists from the University of Wisconsin-Madison reports that it has developed methods for recombining segments of DNA within stem cells.

By bringing to bear the technique, known in scientific parlance as homologous recombination, on DNA in human embryonic stem cells, it is now possible to manipulate any part of the human genome to study gene function and mimic human disease in the laboratory dish.

"Indeed, homologous recombination is one of the essential techniques necessary for human ES cells to fulfill their promise as a basic research tool and has important implications for ES cell-based transplantation and gene therapies," write Wisconsin researchers Thomas P. Zwaka and James A, Thomson, the authors of the new study.

The technique has long been used in the mouse and is best known in recent years for its use to generate mice whose genomes have been modified by eliminating one or more genes. Known as 'knockouts,' genetically altered mice have become tremendously important for the study of gene function in mammals, and have been used to explore everything from the underlying mechanisms of obesity and other conditions to the pinpointing of genes that underpin many different diseases.

Significant differences between mouse and human embryonic stem cells have, until now, hampered the application of the technique to human ES cells, according to Zwaka, the lead author of the Nature Biotechnology report and a research scientist working in the laboratory of James Thomson. Thomson was the first to isolate and culture human embryonic stem cells nearly five years ago.

"This is a big benefit for the human ES cell field,"

Contact: Thomas P. Zwaka
University of Wisconsin-Madison

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