In summary, the likelihood of recombination of the vector SAX itself 
leading to a replication- competent retrovirus in vivo is low for the following 
reasons: (1) the deletion in the vector is large requiring all the gag. pol and 
env regions to be exchanged. (2) the endogenous host sequences available for 
recombination appear to be defective. (3) there appears to be little homology 
between the LTRs of the Moloney MuLV and the endogenous human retroviruses. (4) 
homologous recombination is infrequent in mammalian cells, and (5) the product 
of the human sequences would have to recognize the vector's packaging signal 
for virion formation. 
The probablity that the patient's cell can act as a producer cell of the 
vector is also very low. To date, all human endogenous retroviral sequences 
studied have been defective and the defects are in regions that would not be 
complemented by the inserted vector (i.e., outside the LTR's). This conclusion 
is also supported by the inability to isolate infectious human endogenous 
retrovi ruses. 
III. Malignant potential for retroviral- mediated gene therapy 
Retroviruses are known to cause tumors in animals. The possibility that 
infection with a retroviral vector will also cause malignant transformation in 
an infected cell is real, but the frequency with which this event might occur 
Is unknown. There are multiple factors that need to be considered in trying to 
determine the malignant potential of retroviral vectors. 
Retroviruses causing tumors can be grouped into two different classes. 
The acutely transforming retroviruses contain oncogenes within their viral 
genome that lead to cellular transformation of susceptible cells. Infected 
animals develop malignancy in a short period of time (2-4 weeks) and at a high 
efficiency. The second class are the slowly transforming retroviruses. These 
viruses do not contain oncogenes but rather transform cells by inserting within 
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Recombinant DNA Research, Volume 12 
