HUMAN GENE THERAPY PROTOCOL 
RIBOZYME GENE THERAPY FOR HIV-1 INFECTION 
AN OPEN-LABEL, CONTROLLED, PHASE 1 CLINICAL TRIAL TO EVALUATE IN HIV-1 
INFECTED HUMANS THE SAFETY AND EFFECTS OF AUTOLOGOUS LYMPHOCYTES 
TRANSDUCED WITH A RIBOZYME THAT CLEAVES HIV-1 RNA. 
1. INTRODUCTION 
1.1 Project Objectives 
The principal objectives of this phase one, controlled trial of somatic cell gene transfer 
into HIV-1 infected humans are: 
A) to determine the safety of infusing autologous lymphocytes that have been transduced 
ex vivo with a retroviral vector bearing an HIV-1 leader sequence hairpin ribozyme. 
B) to compare in vivo in each patient the kinetics and survival of ribozyme-transduced 
cells with a separate aliquot of cells transduced with a control vector (identical 
except for the ribozyme cassette). 
C) to determine the in vivo expression of the ribozyme in transduced lymphocytes. 
D) to establish whether host immune responses directed against the transduced cells will 
occur in vivo. 
E) to make preliminary observations on the effects of gene therapy with an anti-HIV-1 
ribozyme on in vivo viral mRNA expression, viral burden and CD4+ lymphocyte 
levels. 
1.2 Background & Rationale for Gene Therapy of HIV Infection 
A. The Nature and Magnitude of the Problem . HIV-1 infection causes progressive 
depletion of CD4 + T lymphocytes and, after a period of clinical latency averaging 7-12 
years, the clinical syndrome of AIDS in the overwhelming majority of patients. Twelve 
years after the first description of AIDS, the global pandemic continues to grow. Despite 
Protocol 
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