bone marrow cells will undergo safety testing prior 
to infusion (Table 3) . 
7.4) Safety Issues 
A detailed and referenced discussion of safety 
issues in RMGT is included in Appendix 8 . A 
synopsis of that paper is presented below. 
7.41) Replication competent virus 
Since we are proposing to transfer 
genetic material in a retroviral vector, 
what potential hazards does this pose to 
the patient? We believe that under the 
conditions of this protocol the procedure 
is essentially safe. The LNL-6 vector 
has been modified so that it is no longer 
carries any viral genes. The only coding 
genetic material that will be transferred 
to the patient's cells will be the marker 
gene (neo R ) . Since LNL-6 has no 
remaining viral genes, it is incapable of 
producing the virion proteins necessary 
to package its RNA into an intact 
infectious virus. 
Since retroviral vectors are replication- 
detective, their genome must be 
"packaged" into a virion so that they may 
transfer their genetic material to the 
target cell. This is accomplished by use 
of a "packaging cell line" which supplies 
the necessary gag, pol and envelope 
proteins for virion formation (Figure 2) . 
The cell to be used, PA317, contains a 
modified murine leukemia virus (MLV) 
genome with intact gag, pol and envelope 
genes, but with deletions which make the 
virus incapable of inserting its RNA 
genome into a virion. Thus, the 
patient's cells are never exposed to a 
replication-competent virus, but only a 
viral coat within which is contained the 
replication-defective retroviral vector. 
The LNL-6/PA3 17 combination has been 
tested extensively for replicating 
retrovirus, which could theoretically 
develop by recombination between vector 
and viral sequences in the packaging cell 
lines. To date, the multiple 
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