Recombinant DNA Advisory Committee - 09/9-10/93 
Investigator Response— Dr. Cohen 
Dr. Miller stressed that the viability test on the irradiated cells should be performed 
using cell numbers that correlate to a patient dose, i.e., 10 8 cells. Dr. Cohen agreed to 
comply with this stipulation. Dr. Miller suggested RCR safety testing should be 
performed by co-cultivation with human target cells rather than mouse cells that may be 
resistant to infection by human RCR. The activated RCR can be assayed by a neo R 
colony assay since it will package the vector with the neo R gene. Dr. Q)hen agreed to 
this suggestion. 
In response to Dr. Haselkom's question about Dr. Richards no longer being at the 
University of Chicago, Dr. Cohen stated that Dr. Richards has joined the faculty of the 
University of Illinois and will continue to collaborate on this project. 
On the Informed Consent document issue, Dr. Cohen agreed to the RACs 
recommendation about a request for autopsy. 
Committee Motion 
A motion was made by Dr. Smith and seconded by Ms. Buc to approve the protocol 
contingent on the review and approval of the following stipulations by the primary 
reviewers and by Dr. Miller: (1) submit data demonstrating that the proposed dose of 
radiation effectively inhibits viability using the number of cells proposed for a single 
patient dose, (2) submit colony assay data demonstrating lack of RCR using irradiated 
transduced melanoma cells, and (3) submit revised language for the Informed Consent 
document that explains how consent for autopsy will be obtained, i.e., invoking the 
Uniform Anatomical Gift Act or requesting assent from the patient's relatives. The 
motion passed by a vote of 17 in favor, 0 opposed, and no abstentions. 
XI. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: A PHASE I CLINICAL TRIAL TO 
EVALUATE THE SAFETY AND EFFECTS IN HIV-1 INFECTED HUMANS OF 
AUTOLOGOUS LYMPHOCYTES TRANSDUCED WITH A RIBOZYME THAT 
CLEAVES HIV-1 RNA/DRS. WONG-STAAL AND POESCHLA 
Review-Dr. Straus 
Dr. Walters called on Dr. Straus to present his primary review of the protocol submitted 
by Drs. Flossie Wong-Staal, Eric Poeschla, and David Looney of the University of 
California, San Diego, La Jolla, California. This protocol is a Phase I study of a 
retrovirus construct containing a ribozyme insert that when expressed is capable of 
cleaving HIV transcripts and diminishes virus replication and spread. Ribozymes are 
potentially therapeutic RNA molecules that contain antisense sequences for specific 
recognition and RNA-cleaving enzymatic activity. The investigators have demonstrated 
that human T cell lines and primary peripheral blood T cells transduced with the hairpin 
ribozyme that cleaves HIV-1 RNA in the 5' leader sequence are intracellularly 
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Recombinant DNA Research, Volume 18 
