Researchers have for the first time demonstrated partial success of "therapeutic cloning" in an animal. In a virtuoso display of cutting-edge techniques, a team combined cloning, embryonic stem cells, and gene therapy to treat immune-deficient mice with genetically tailored stem cells.
The first two steps of the experiment were not unusual. William Rideout and colleagues in the labs of Rudolf Jaenisch and George Daley at the Massachusetts Institute of Technology's Whitehead Institute for Biomedical Research first cloned a mouse that had a genetic immune deficiency by inserting the nucleus of a cell from its tail into an enucleated mouse egg. They grew the embryo into a blastocyst, the stage where cells are then extricated in order to cultivate embryonic stem (ES) cells. Then they used standard gene therapy to correct the genetic defect in the ES cells, which were cultivated into blood stem cells.
The next stage was the big challenge: reintroducing the doctored cells into the animal's body to treat its disease. While most of the mouse's immune system was disabled, it still would reject the embryonic cells--apparently because they are different from adult cells and therefore recognized as abnormal. The scientists discovered, however, that they could get around this problem by adding a gene, HOXB4, that is crucial for blood development. As hoped, the gene caused the embryonic cells to develop into adult hematopoietic (blood-forming) cells--with the result that some were successfully "engrafted" into the immune system, restoring a "modest degree" of immune function. The scientists report their findings in the two papers, published online 8 March in Cell.
Humans also have the HOXB4 gene, and it is possible that tinkering with the pathway could offer the key to successful incorporation of embryonic blood cell precursors in humans as well, says Michael Kyba, first author on one of the papers. The ability to do this in humans "would be a major step toward therapeutic cloning," says geneticist Frederick Alt of Harvard Medical School in Boston.