Gene therapy using bone marrow transplantation: a 1990 update

The use of recombinant retroviruses for gene transfer into the haematopoietic tissue in vivo is still a new area of research. The initial results of in vitro studies were very exciting. In contrast, the early in vivo studies in mice were somewhat disappointing because of the transient and low levels of expression of the transferred gene. Recently, however, better results have been obtained in the murine system in vivo. New packaging cell lines have been constructed, which are safer and still efficient. Better vectors have been designed. Thus, significant levels of expression of the transgene have been achieved in murine long-term transplant recipients. However, the results obtained so far in large animal studies are still disappointing. It should be emphasized that further progress must be based on a simple overall strategy involving better understanding of the functioning of the gene to be transferred by gene expression studies, design of vectors carrying a fully active and correctly regulated minilocus and better knowledge of the biological properties of the target cells, the haematopoietic stem cells.