preselection of infected cells with G418 prior to transplantation, and/or 
Infection of hematopoietic progenitors in the presence of growth factors, e.g. 
IL-3, 80-100% of the hematopoietic progenitors transplanted into irradiated 
mouse recipients for both short and long term hematologic reconstitution have 
carried the vector (Keller et al.. 1985; Dick et al.. 1985; Lemishka et al.. 
1986; Magi i et al . 1987, and Table la). 
Studies by our own group : A number of vectors have been used. 
Including N2 and a series of N2-derived vectors containing an ADA cDNA with one 
of a number of different promoters (Eglitis et al.. 1985; Kantoff et al.. 1986; 
copies supplied In Appendix B). Experiments performed in our laboratory either 
with or without IL-3 at the time of Infection of mouse bone marrow have 
demonstrated an efficiency of vector gene transfer into mouse bone marrow of 
between 50-90% (Table la). 
B. Stem Cell Transduction and Vector Stability ; 
Literature review: Several Investigators have demonstrated that long 
term reconstitution of mice could be accomplished with only a few stem cell 
clones carrying vector sequences (Williams et al.. 1984; Keller et al.. 1985; 
Lemischka et al.. 1985; Dick et al.. 1985). The patterns of proviral 
Integration suggested that the transduced stem cells could give rise to both 
myeloid and lymphoid lineages or, alternatively, might be restricted to either 
myeloid or lymphoid differentiation. Moreover, proviral sequences remained 
stably Integrated 4-6 months following reconstitution. In one study, changes 
In the Intensity of particular DNA bands on Southern blots was interpreted as 
reflecting the sequential activation of different hematopoietic progenitor 
cells during the life of the animal. Secondary reconstituents (obtained when 
cells from the primary animal are used to reconstitute another lethally 
Irradiated animal) continued to carry proviral sequences in the same pattern as 
[251 
Recombinant DNA Research, Volume 12 
