the In vitro studies, it is not possible to select for expressing cells in the 
whole animal. Thus in monkeys (which are not ADA-deficient) there is no 
positive selection pressure for cells carrying and expressing the introduced 
genes. Vectors carrying the DHFR gene have been constructed in order to 
provide an in vivo selective pressure. However, none of these vectors has yet 
provided convincing evidence of in vivo selective advantage. 
It will be Important In future gene transfer efforts using a large animal 
model (l.e.. the monkey) to achieve better Infection rates. A larger 
proportion of cells carrying the human ADA vector sequences will facilitate the 
analysis of Integration and stability In long term reconstituted animals. Our 
laboratories are presently Investigating methods: a) to Increase the rate of 
infection and b) to separate bone marrow cells to enrich for plurlpotent stem 
cells with self-renewal capacity. It Is also Important to achieve higher 
overall levels of vector-derived ADA expression which Is maintained In long 
term reconstituted animals. We are developing and analysing new vectors 
containing the human ADA gene with a variety of Internal promoters, together. 
In some cases, with the elimination of the bacterial Neo gene (which was 
Initially Included as a means of testing viral titer In producer cell lines) on 
p 
the possibility that the presence of the Neo gene could Interfere with 
expression of the human ADA gene. 
Review 
Retroviruses have been successfully employed to introduce functioning 
genes Into cells In culture as well as whole organisms. This review will focus 
on retroviral vectors derived from the Moloney strain of murine leukemia virus 
(Mo-MuLV) which have been modified by deleting the viral structural genes and 
replacing them with one or. In some cases, two foreign genes. Expression of 
the Introduced gene(s) may be modulated by promoter elements contained in the 
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Recombinant DNA Research, Volume 12 
