Gene therapy: Principles and applications to hematopoietic cells

Abstract

Ever since the development of technology allowing the transfer of new genes into eukaryotic cells, the hematopoietic system has been an obvious and desirable target for gene theraphy. The last 10 years have witnessed an explosion of interest in this approach to treat human disease, both inherited and acquired, with the initiation of multiple clinical protocols. All gene therapy strategies have two essential technical requirements. These are: (1) the efficient introduction of the relevant genetic material into the target cell and (2) the expression of the transgene at therapeutic levels. Conceptual and tehnical hurdles involved with these requirements are still the objects of active research. To date, the most widely used and best understood vectors for gene transfer in hematopoietic cells are derived from retroviruses, although they suffe from several limitations. However, as gene transfer mechanisms become more efficient and long-term gene expression is enhanced, the variety of disease that can be tackled by gene theraphy will continue to expand. However, until the problem of delivery and subsequent expression is adequately resolved, gene theraphy will not realize its full potential. The first part of the review gives an overview of the gene delivery technology available at present to transfer genetic sequences in human somatic cells. The relevance of the hematopoietic system to the development of gene therapy strategies as well as hematoppietic cell-based gene therapy is discussed in the second part.