What steps have been taken In designing the vector to 
mlnlirize pathogenicity? 
To minimize pathogenicity, the SAX vector contains only the portion of the 
viral genome needed for integration and packaging, i.e., the LTR and 
approximately 1 kb of 5' non-LTR sequence. By deleting the pol . env and almost 
all of the ga£ sequences, the virus particle does not contain the information 
needed for replication. Therefore, after the viral particle infects a cell it 
cannot replicate. Only if the infected cell already contains the machinery for 
viral production can the information in the SAX vector be passed on to other 
cells. Although the human genome has not yet been shown to have the 
information needed for producing infectious retroviral particles, it still 
cannot be stated with certainty that, even in the absence of helper virus, only 
the bone marrow cells would receive the vector. In the absence of replication- 
competent virus, however, there theoretically should be no spread of the vector 
to other tissues. Including the germ line. The lack of viremia should also 
greatly decrease the risk of malignancy by insertional mutagenesis (see below). 
How much effect a low level of replication-competent virus would have in vivo 
Is uncertain. Furthermore, it is not known what would happen if the patient be- 
came Infected with a human retrovirus (e.g.. HTLV-I or HIV). Perhaps these parti- 
cles could also package the vector transcript and spread it throughout the body. 
What laboratory studies have been performed to check for 
pathogenicity, and what Is the sensitivity of the 
analyses? 
None of the monkeys studied have displayed any overt signs of pathology 
that could be directly related to retrovirus infection: viremia, bone marrow 
pathology, or tumors. Our oldest two (who also had the highest levels of human 
ADA) are now 1 1/2 years post-transplant. However, a more comprehensive safety 
study In which a large dose of replication-competent viral particles is being 
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Recombinant DNA Research, Volume 12 
