Safety of retrovirus gene therapy, Temin. 
Secondly, the new therapy should not do harm to health care workers and other 
care givers including the patients’ families. Possible types of harm to the persons in close 
contact with patients undergoing retrovirus somaric gene therapy are infecdon by new 
viruses resulring from the therapy, legal liability, coping with medical and psychological 
complicauons in the patients, and bad publicity. 
Thirdly, the new therapy should not result in harm to the general population. 
We must consider the possibility of formation of a new virus during somatic gene therapy 
of human disease with retrovirus vectors, the costs of such therapy, and the possible 
evolutionary effects of such therapy such as infection of the patient’s germ-line. 
B. Characteristics Of The Safest Possible Retrovirus Vector System For Human 
Somatic Gene Replacement Therapy 
A retrovirus vector-helper cell system, like any other genetic system, is subject 
to mutation and selection. Retrovirus vectors have certain intrinsic properties which 
make them good vectors, but they also have other intrinsic properties which introduce 
potential problems to their use as vectors. These potential problems can not be removed 
by better design of the vectors. 
The safest possible retrovirus vector system involves a vector with the minimal 
amount of retrovirus sequences, that is, only R-U5-ar;R-PBS-E-insert(s)-PPT-crrL-R 
(Figure 1). The vector is produced by a helper cell containing coding sequences from the 
homologous retrovirus, but no control or other c/j-acting sequences from the homologous 
retrovirus, and thus no sequences homologous with those in the vector (Figure 1 and ear- 
lier Chapter, see also Weiss et al.,jl98^,1985; Temin, 1986b; Miller and Buttimore,1986). 
Such a vector-helper cell combination would remove any possibility of homologous 
recombination between the vector and the helper cell and, thus, greatly decrease the 
chance of recombination to form a replication-competent retrovirus. However, even with 
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