Progress in the use of gene transfer methods to treat genetic blood diseases

A report by French physician-scientists suggests a successful application o f gene transfer methods in the treatment of two children with severe combin ed immunodeficiency (SCID) due to defective interleukin 2 receptor common g amma chain. The protocol used in this clinical trial was derived from a num ber of preclinical and basic studies leading to improved transduction of he matopoietic stem and primitive progenitor cells using retrovirus vectors. T hese improvements have also been shown to impact transduction of a long-liv ed progenitor cell in a chemotherapy protocol in cancer patients. The impro ved results of these human trials come during a period of increased scrutin y and criticism of human gene therapy trials, due, in part, to significant toxicities in some trials using adenovirus-based vectors. The potential eff icacy versus toxicity of phase I trials of human gene therapy is also under question. After many years of research, however, there appears to be real evidence that genetic diseases may be successfully treated by gene transfer techniques. Future clinical studies should be based on continued progress in the understanding of the toxicology of gene delivery systems, vector tec hnology, and target cell manipulation.