Safety of retrovirus gene therapy, Temin, 
hypothetical replication-competent retrovirus formed by recombination with the vector is 
as unlikely as the formation of the virus in the first place. 
Whether such a hypothetical virus could spread to other people is also hard to 
evaluate. We know little about the determinants of spread of retroviruses between 
organisms. However, retroviruses are usually not very easily transmitted, for example, 
even HIV, the vims causing AIDS, is not very contagious. ^ 
■ — i 
In summary, recombination to form a replication-competent retrovirus is ex- 
tremely unlikely, and if a replication-competent retrovirus was formed by recombination, 
it is extremely unlikely that it would have any observable biological effect. 
2. other potential problems 
Rodent cells are known to contain endogenous sequences that are parasitic on 
retroviruses in the sense that the RNA transcribed from these endogenous sequences can 
be packaged in retrovirus virions, introduced into recipient cells by infection, and form a 
provims (Sotye and Coffin, 1985). One of these sequences, VL30 sequences, is produced 
in high quantities from mouse helper cells, psi-2 cells (Keshet,1985). The consequences 
of this pseudotyping in somatic gene therapy of human disease with retrovirus vectors 
would be the introduction of many rodent endogenous sequences into the bone marrow of 
the patient at the same time the vector sequences are introduced. There are three possible 
effects of these sequences: mutation, expression, and recombination. The effects of inser- 
tional mutation by VL30-like sequences are no worse than discussed above for the vector 
itself and so can be ignored. So far little is known about the coding capacity of these 
sequences; so the effects of their expression cannot be evaluated directly. However, there 
arc about 100 copies of VL30 sequences in the mouse genome with no apparent ill ef- 
fects. Most worrisome is the possibility that these sequences could recombine with 
human endogenous sequences and/or vector sequences to form a new replication- 
Recombinant DNA Research, Volume 12 [385] 
