Human Cene Therapy 
cells) can be extracted from the body, grown in culture to allow 
insertion of exogenous genes, and then successfully reimplanted into 
the patient from whom the tissue was taken. In the future, as more 
is learned about how to package the DNA and to make it tissue- 
specific, the intravenous route would be the simplest and most 
desirable. However, attempting to give a foreign gene by injection 
directly into the bloodstream is not advisable with our present state 
of knowledge since the procedure would be enormously inefficient 
and there would be little control over the DNA’s fate. 
Studies are considerably more advanced with bone marrow than 
skin cells as a recipient tissue for gene transfer. Bone marrow consists 
of a heterogeneous population of cells, most of which are committed 
to differentiate into red blood cells, white blood cells, platelets, and 
so on. Only a small proportion (0.1 to 0.5 percent) of nucleated 
bone marrow cells are stem cells (that is, blood-forming cells that 
have not yet differentiated into specific cell types and which divide 
as needed to maintain the marrow population). In gene therapy, it 
would be these rare, unrecognizable stem cells that would be the 
primary target. Consequently, a delivery system useful for gene ther- 
apy must be efficient. 
Several techniques for transferring cloned genes into cells have 
been developed (Anderson, 1984). Each procedure is valuable for 
certain types of experiments, but none can yet be used to insert a 
gene into a specific chromosomal site in a target cell. At present the 
most promising approach for use in humans employs retrovirus- 
based vectors carrying exogenous genes. 
Vectors derived from retroviruses possess several advantages as a 
gene delivery system. First, up to 100 percent of cells can be infected 
and can express the integrated viral (and exogenous) genes. Second, 
as many cells as desired can be infected simultaneously; 10 6 to 10 7 
is a convenient number for a simple protocol. Third, under appro- 
priate conditions, the DNA can integrate as a single copy at a single, 
albeit random, site. Finally, the infection and long-term harboring 
of a retroviral vector usually does not harm cells. Several retroviral 
vector systems have been developed; those projected for human use 
at the present time are constructed from the Moloney murine (mouse) 
leukemia virus. Evidence obtained from studies with experimental 
animals and in tissue culture indicates that retroviruses can be used 
as a reasonably efficient delivery system. 
An ideal delivery system would be tissue-specific. When a genetic 
disorder is in the blood cells, the isolated bone marrow can be 
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