Although considerable progress has been made in defining the genetics of autoimmune disease, nearly all of the major systemic autoimmune diseases are highly complex. multigene disorders, even in animal models. In comparison with single gene disease, such as cystic fibrosis or alpha 1-antitrypsin deficiency, it may prove considerably more difficult to correct genetically complex autoimmune disorders using standard gene therapy approaches. However, there may be reason for cautious optimism because inhibition of a single cytokine (TNF-α) can have a significant beneficial effect in the treatment of a multigenic autoimmune disorder (RA). At least in mice, retroviral transduction of Foxp3 has been shown to convert naive T cells into cells that phenotypically and functionally resemble Treg. Whether this approach will be applicable to the therapy of autoimmune disease remains to be determined.