Chapter 32. Perspectives on Human Gene Therapy

Publisher Summary A major obstacle to the treatment of human diseases is the inability to express genes stably at specific sites. Progress in the regulation of eukaryotic transcription and viral gene expression has made it possible to address fundamental questions relevant both to basic biology and to human diseases. Gene transfer technology has also provided access to a variety of recombinant gene products that can be applied to clinical medicine for diagnostic and therapeutic purposes. Developments and future potential of this technology and its application to human gene therapy are discussed in this chapter. Potential host cells may be derived from the bone marrow, liver, lymphoid system, central nervous system (CNS), and lung. This chapter discusses the new area of gene therapy as a representative example of the potential for gene therapy to impact human diseases. This technology involves the insertion of normal genes into somatic cells to correct an inherited or acquired disorder through the synthesis of missing or defective gene products. Methods have been employed to introduce recombinant genes into the host cells of different organ systems. Efforts toward human gene therapy have focused on providing the correct gene product. The chapter discusses gene transfer vectors, gene transfer into the vasculature, cell-mediated gene transfer, gene transfer in vivo and its biologic effects, and future directions in the application of gene therapy to systemic drug delivery. In any vessel, a limited number of endothelial cells are available. However, it would be necessary to transduce a much larger number of cells to make sufficient gene product to detect it circulating in the blood by transducing cells in the capillary circulation.