Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy.Rideout III, W. M. et al. Cell 109, 17–27 (2002)
In this proof-of-principle study, Rideout et al. have tested whether a genetic defect in somatic cells can be corrected using a combination of therapeutic cloning and gene therapy. They began by deriving ES cells from cloned blastocysts generated from the transferred nuclei of Rag2−/− mice. The Rag2 defect in these cells was then corrected by gene targeting, and mice were derived from the corrected cells by tetraploid complementation. These mice developed with normal B- and T-cell populations; moreover, when their bone marrow cells were transferred to Rag2−/− mice, they restored immune function in the transplanted mice. However, haematopoietic stem cells derived in vitro from the corrected ES cells were unable to repopulate the haematopoietic compartment in Rag2−/− mice because of natural-killer-cell-mediated graft rejection, raising the point that even genetically identical cells derived by therapeutic cloning can still face host-mediated transplantation barriers.
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