An improved method of nuclear transfer involving the transplantation of
donor cell nuclei into enucleated oocytes of a species different from the
donor cell is provided. The resultant nuclear transfer units are useful
for the production of isogenic embryonic stem cells, in particular human
isogenic embryonic or stem cells. These embryonic or stem-like cells are
useful for producing desired differentiated cells and for introduction,
removal or modification, of desired genes, e.g., at specific sites of the
genome of such cells by homologous recombination. These cells, which may
contain a heterologous gene, are especially useful in cell
transplantation therapies and for in vitro study of cell differentiation.