Since the development of methods for gene transfer in mammalian cells
about 15 years ago and in particular after the introduction of those with
high efficiency such as viral systems the use of genetically manipulated
somatic cells for therapy has continuously been such an attractive topic
that it has been frequently reviewed (Anderson 1984; Kantoff et al. 1988;
Friedmann 1989; Verma 199o; Miller 1992; Anderson 1992; Mulligan 1993;
Counoyer and Caskey 1993). Originally, the main targets for gene therapy
were inherited monogenetic recessive disorders. Examples are diseases
with defects in genes encoding adenosine deaminase (severe combined
immunodeficiency), 13-globin (thalassemia), factor VIII, IX (hemophilia),
cystic fibrosis transmembrane regulator (cystic fibrosis), glucocerebrosidase
(Gaucher's disease), [3-glucuronidase (mucopolysaccharidosis), lowdensity
lipoprotein (LDL)-receptor (hypercholesterolemia) or dystrophin
(Duchenne muscular dystrophy). In recent years, however, the major focus
of gene therapy approaches has turned to acquired diseases, mainly cancer.
Several reasons may account for that: (a) cancer patients are numerous,
but patients with most genetic defects are rare, (b) it is still difficult to
obtain a regulated and prolonged expression of transgenes in vivo, (c)
with few exceptions such as the hematopoietic system primitive stem cells
able to long term reconstitute the respective organ are not yet well characterized,
and (d) cost/benefit calculations (side effects versus therapeutic
benefit) seem to favor cancer for gene therapy over genetic diseases.