cynomologous macaque and rhesus monkeys with amphotropic murine helper virus 
(41), a broad consensus exists that stringent testing for helper virus is necessary for 
human trials (2,42,55) and we plan the comprehensive studies now standard in gene 
therapy protocols (explained in part B of POTENTIAL RISKS & RISK MANAGEMENT 
PROCEDURES be tow). 
Two other trials approved for treatment HIV disease have guided our preparation of this 
proposal. One is a marker study involving retroviral vector-mediated transfer of a 
marker gene to HIV antigen-specific T cells (2). The other study is a protocol involving 
retroviral vector transfer of a trans-dominant rev protein to peripheral blood 
lymphocytes of HIV-infected subjects (G. Nabel, personal communication). 
We therefore believe that these considerations and the potent anti-viral effects we have 
observed in primary T cells provide ample justification for phase I testing of the safety 
and effects of this ribozyme in human subjects with HIV infection. 
2 . FACILITIES 
The in vitro manipulations of patient lymphocytes, including transduction, selection and 
expansion of cells will be performed in the UCSD Clinical Sciences Building, a new 
building with a full range of needed equipment, including two large Biosafety Level 3 
(BL-3) containment facilities, tissue culture facilities and computer analytic 
capabilities. One floor of the building (approxamately 5000 square feet) is reserved for 
sole use by the Wong-Staal laboratory and one of the investigators (EMP) is supervisor 
of the BL-3. Manipulations of HIV-infected cells after harvesting and prior to re- 
infusion will be carried out with adherence to standard BL-3 containment practices with 
which the investigators have many years of cumulative experience. 
Evaluation of patients, harvesting of patient lymphocytes and re-infusion of gene- 
transduced lymphocytes will be carried out in the UCSD Clincal Research Facility, the 
UCSD Medical Center and the Veterans Administration Medical Center, San Diego, CA. 
3. ESTIMATED DURATION OF STUDY 
One year of close clinical follow-up and laboratory analyses is planned for the primary 
experimental observations . We plan to continue long-term follow-up of patients with 
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