CURRENT STATUS OF GENE-TRANSFER INTO AUTOLOGOUS HEMATOPOIETIC-CELLS

Gene therapy is a new field of biomedical research just entering clinical practice. Recombinant retroviruses are at present the best vectors for gene transfer into a permanently dividing tissue like the hematopoietic tissue. The ex vivo strategy consists of an autologous transplantation of genetically modified cells. Although the hematopoietic tissue can be manipulated with comparative ease, its development and its structure are rather complex. Therefore, the different sources of hematopoietic tissue and the diverse cell types represent a wide array of targets for gene transfer. In vivo studies in mice have shown that the hematopoietic stem cells can be efficiently transduced by retroviral vectors carrying therapeutic genes. In contrast, preclinical studies in large outbred animals indicate that only a small proportion of stem cells can be transduced, although much better results can be obtained with primitive progenitors detectable in vitro. However, some clinical trials have already shown interesting and useful results.