It'. French Anderson 
treated. But no other tissue (except skin cells) can be removed, 
treated, and replaced at present. Since many viruses arc known to 
infect only specific tissues (that is, to bind to receptors that are 
present only on certain cell types), a retroviral particle containing 
a coat that recognizes only human blood-forming cells would permit 
the retroviral vector to be given intravenously with little danger that 
cells other than those in the marrow would be infected. In the future, 
such specificity could permit the liver and brain, for example, to be 
treated individually. In addition, the danger of inadvertently infecting 
germ cells could be eliminated. One problem, however, is that cell 
replication appears to be necessary for retrovirus integration. It 
would not be possible to infect nondividing brain cells, for example, 
so far as we now know. 
The optimal system not only would deliver the vector specifically 
into the cell type of choice, but would also direct the vector to a 
predetermined chromosomal site. Specific insertion into a selected 
site on a chromosome can be achieved in lower organisms but has not 
yet been possible in mammals. 
l:\yression 
In order for gene therapy to be successful, there must be appropriate 
expression of the new gene in the target cells. Even when a delivery 
system can transport an exogenous gene into the DNA of the correct 
cells of an organism, it has been a major problem to get the integrated 
DNA to function. A vast array of cloned genes have been introduced 
into a wide range of cells by several gene transfer techniques. ‘Normal’ 
expression of exogenous genes is the exception rather than the rule. 
Expression of exogenous genes carried by retroviral vectors into 
intact animals via treated bone marrow cells has been reported by 
three laboratories. Two studies demonstrated the expression of an 
antibiotic resistance gene in mice (Joyner et al., 1983; Williams et al., 
1984). The most extensive data, however, are from studies with the 
enzyme HPRT (Miller et al., 1984; Willis et al., 1984). A homozygous 
Lesch-Nyhan (LN) lymphoblast (white blood cell) line, which lacks 
a functional HPRT gene, was used to demonstrate that an HPRT - 
human blood-forming cell could be corrected by a retroviral vector 
containing an active HPRT gene. In a corollary study, viral particles 
containing the HPRT-vector were used to infect mouse bone marrow 
cells that were then injected into lethally irradiated mice. Both 
human HPRT protein and chronic production of HPRT-vector par- 
ticles were detected in the blood-forming tissues of the mice. These 
Recombinant DNA Research, Volume 12 
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