3198 Biochemistry: Yu el al. 
/‘roc. Noll. Acad. Sci. USA S3 (IVH6) 
representing a low percentage of cells in which the LTR is 
fully active transcriptionally. 
SIN vectors should be especially useful to introduce genes 
into animals in experiments in which the regulated expression 
of the transduced gene is under study. This was demonstrated 
in this report by using the hybrid gene containing the 
inducible human MT promoter fused to the c -fas gene. 
F-TK-N (Fig. 4). The regulated synthesis of the authentic 
c-fos RNA transcripts in the infected cells (Fig. 4 C) as well 
as the analysis of the proviral structure (Fig. 45) demonstrate 
that the SIN vector used in this experiment can transfer the 
nonselectable gene to the target cells in a stable manner 
without rearrangements involving the loss of the transduced 
gene. In this regard. SIN vectors differ from previous 
retroviral vectors used to transduce whole genes that were 
unstable, resulting in (he loss of the nonselected transduced 
gene in the infected cells (refs. 26-28: unpublished results). 
It is possible, although unlikely, that the MT-c-/rw gene 
possesses special features that allow its stable transmission 
via a retrovirus vector. The ability of SIN vectors to 
transduce, in a stable manner, genes other than those studied 
so far (c-fos: Fig. 4) has to be demonstrated before the general 
utility of these vectors can be established. 
Retrovirus vectors are currently being used to design 
somatic cell human gene therapy procedures (13) using bone 
marrow cells as the target cells for infection (refs. 7-11; 
unpublished results). One of the safety concerns associated 
with this procedure is the potential activation of cellular 
oncogenes through the enhancer and promoter sequences 
encoded in the viral LTRs. By using SIN vectors, the viral 
enhancer and promoter sequences will be lost from both 
LTRs in the infected cell, thus reducing the possibility of 
activating adjacent cellular oncogenes. 
We thank Nancy Plum and Cathy Magruder for assistance with the 
manuscript. This work was funded in part by American Cancer 
Society Grant M-116B and March of Dimes Grant 1-856. U.R. is a 
recipient of a European Molecular Biology Organization postdoc- 
toral long-term fellowship. T.V.R. is a recipient of a Deutsche 
Akademischer Austauschdienst predoctoral fellowship. 
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Recombinant DNA Research, Volume 12 
