Single virus used to convert adult cells to embryonic stem cell-...( CAMBRIDGE Mass. (Dec. 15 2008) Whit...)

CAMBRIDGE, Mass. (Dec. 15, 2008) Whitehead Institute researchers have greatly simplified the creation of so-called induced pluripotent stem (iPS) cells, cutting the number of viruses used in the reprogramming process from four to one. Scientists hope that these embryonic stem-cell-like cells could eventually be used to treat such ailments as Parkinson's disease and diabetes.

The earliest reprogramming efforts relied on four separate viruses to transfer genes into the cells' DNA--one virus for each reprogramming gene (Oct4, Sox2, c-Myc and Klf4). Once activated, these genes convert the cells from their adult, differentiated status to an embryonic-like state.

However, this method poses significant risks for potential use in humans. The viruses used in reprogramming are associated with cancer because they may insert DNA anywhere in a cell's genome, thereby potentially triggering the expression of cancer-causing genes, or oncogenes. For iPS cells to be employed to treat human diseases, researchers must find safe alternatives to reprogramming with such viruses. This latest technique represents a significant advance in the quest to eliminate the potentially harmful viruses.

Bryce Carey, an MIT graduate student working in the lab of Whitehead Member Rudolf Jaenisch, spearheaded the effort by joining in tandem the four reprogramming genes through the use of bits of DNA that code for polymers known as 2A peptides. Working with others in the lab, he then manufactured a so-called polycistronic virus capable of expressing all four reprogramming genes once it is inserted into the genomes of mature mouse and human cells.

When the cells' protein-creating machinery reads the tandem genes' DNA, it begins making a protein. However, when it tries to read the 2A peptide DNA that resides between the genes, the machinery momentarily stops, allowing the first gene's protein to be released. The machinery then moves on to the second gene, creates th
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