"The big issue is how to replace these viruses," said Rudolf Jaenisch, of the Whitehead Institute for Biomedical Research in Cambridge, Mass., who led the new work with co-worker Jacob Hanna and Tim Townes of the University of Alabama Schools of Medicine and Dentistry.
Induced pluripotent stem, or iPS, cells are virtually identical to embryonic stem cells. They can change into all of the more than 200 cell types in the body but are derived from skin, not from embryos. Mouse iPS cells were first derived earlier this year, and scientists reported last month to great fanfare that they had created similar cells from human skin.
The experiment started with the removal of a few skin cells from the tail tips of mice sick with sickle-cell anemia, which can cause painful circulatory problems, kidney failure and strokes.
The researchers converted those cells into iPS cells by infecting them with viruses engineered to change the cells' gene activity so they would resemble embryonic cells.
Using DNA-splicing techniques, the researchers snipped out the small mutated stretches of DNA that cause sickle-cell disease and filled those gaps with bits of DNA bearing the proper genetic code.
Next, researchers treated the corrected iPS cells with another kind of virus, one designed to induce a genetic change that encouraged the cells to mature into bone-marrow cells.
Finally, each mouse that gave up a few skin cells at the beginning of the experiment was given an infusion with the corrected marrow cells created from its own skin cells. Those cells set up permanent residence in the animals' bones and began producing blood cells — the major function of marrow cells — and releasing them by the millions into the circulatory system.
The new blood cells were free of the sickle-cell mutation.
"The mice are cured," Jaenisch said
"I think it is a really exciting proof of principle that clinical applications of iPS cells are technically feasible," said George Daley, a stem-cell researcher at Children's Hospital Boston. "There will be lots of unanticipated setbacks before we end up in the clinic, but this work suggests that we will ultimately get there."
Jaenisch said the success with iPS cells does not mean research on human embryonic stem cells can be dropped, as some opponents of the work have claimed.
"All the progress in this field was only possible because we had embryonic stem cells to work with first," Jaenisch said.
