Gene therapy: principles and applications to hematopoietic cells

Ever since the development of technology allowing the transfer of new genes into eukaryotic cells, the hematopoietic system has been an obvious and de sirable target for gene therapy. The last 10 years have witnessed an explos ion of interest in this approach to treat human disease, both inherited and acquired, with the initiation of multiple clinical protocols. All gene the rapy strategies have two essential technical requirements. These are: (1) t he efficient introduction of the relevant genetic material into the target cell and (2) the expression of the transgene at therapeutic levels. Concept ual and technical hurdles involved with these requirements are still the ob jects of active research. To date, the most widely used and best understood vectors for gene transfer in hematopoietic cells are derived from retrovir uses, although they suffer from several limitations. However, as gene trans fer mechanisms become more efficient and long-term gene expression is enhan ced, the variety of diseases that can be tackled by gene therapy will conti nue to expand. However, until the problem of delivery and subsequent expres sion is adequately resolved, gene therapy will not realize its full potenti al. The first part of this review gives an overview of the gene delivery te chnology available at present to transfer genetic sequences in human somati c cells. The relevance of the hematopoietic system to the development of ge ne therapy strategies as well as hematopoietic cell-based gene therapy is d iscussed in the second part.