Since the first concepts of gene therapy were formulated, the
hemopoietic system has been considered the most natural first target
tissue for genetic manipulation. The reasons for this include the fact
that a very large number of inherited disorders (including some of the
most common disorders, such as the hemoglobinopathies) are disorders of
the hemopoietic system, and the large amount of experience in
hematopoietic transplantation biology. The consequence of this resulted
in the first clinical trial of gene therapy in 1989, where two children
suffering from severe combined immune deficiency (ADA-SCID) were
transplanted with T-cells express- ing adenosine deaminase (the
defective enzyme in patients with this disorder). The partial success of
this treatment was perhaps responsible for undue optimism among those
proposing other gene therapy treatments within the hematopoietic system,
and it has since become clear that there are a number of technical and
biological difficulties to overcome before hematopoietic gene therapy
becomes a mainstream therapeutic strategy. The chapters in this book
evaluate the need for gene therapy in the hematopoietic system, discuss
how efficient gene transfer and expression can be achieved in the target
cells, highlight areas of difficulty to be addressed, and examine a
number of potential applications of the gene therapy approach. The book
begins with a chapter by Testa and colleagues, discussing the various
sources of hematopoietic cells for both transplantation and gene
therapy.
