Recombinant DNA Advisory Committee - 06/7-8/93 
Mento agreed to provide the excipient formulation on a confidential basis. Dr. Post 
proposed this formulation should be reviewed by Dr. Straus and Ms. Grossman. 
Committee Motion 
A motion was made by Dr. Miller and seconded by Dr. Secundy to approve the protocol 
with the following stipulations: (1) the excipient formulation of the retrovirus vector will 
be reviewed by Dr. Straus and Ms. Grossman, and (2) the Informed Consent document 
will include a request for autopsy. The motion passed by a vote of 16 in favor, 0 
opposed, and 2 abstentions. 
XIII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: A MOLECULAR GENETIC 
INTERVENTION FOR AIDS - EFFECTS OF A TRANSDOMINANT NEGATIVE FORM 
OF REV/ DR. NABEL 
Review-Drs. Smith 
Dr. Walters called on Dr. Smith to present his primary review of the protocol submitted 
by Dr. Gary J. Nabel of the University of Michigan Medical Center, Ann Arbor, 
Michigan. Dr. Smith stated that the underlying hypothesis of this protocol is that 
transduction of genes that express a transdominant inhibitory HIV protein into HIV- 
infected and non-infected lymphocytes may reduce productive viral replication in these 
cells. Such action may result in prolonged survival of the transduced cells in vivo in 
patients with HIV. In the long term, it is hoped that prolonged survival could result in a 
beneficial clinical effect for HIV-infected patients by prolonging the latent phase of the 
infection. CD4( + ) cells will be obtained from the peripheral blood of HIV patients, 
stimulated to grow in vitro, and transduced with a retrovirus vector carrying a 
transdominant inhibitory rev gene of HIV (Rev M10). As a control, an aliquot of 
CD4( + ) cells from the same patient will be transduced with a similar vector that 
contains a frameshift mutation at the initiation codon of rev that prevents its expression 
(ARev M10). Both sets of transduced cells will be reinfused in the patient and observed 
for differential rates of survival. The endpoints of the study are: (1) to measure survival 
of the two differentially transduced CD4( + ) cell populations, and (2) to monitor the 
immune status of these patients. The PI has proposed two methods of gene transfer, 
transduction with a retrovirus vector carrying the rev mutant gene and biolistic 
transduction of the mutant gene in a plasmid DNA construct. The latter method would 
avoid many of the safety issues pertaining to retrovirus vectors, but its transduction 
efficiency has not yet been demonstrated. 
Dr. Smith said that the original protocol contained insufficient information about the 
number of patients, the amount of blood necessary for transduction, and an incomplete 
Recombinant DNA Research, Volume 17 
[5711 
