RIBOZYME GENE THERAPY FOR HIV-1 INFECTION 
TABLE OF CONTENTS 
SCIENTIFIC ABSTRACT i 
NON-TECHNICAL ABSTRACT ii 
1. INTRODUCTION 1 
1 .1 . Project Objectives 1 
1.2. Background & Rationale for Gene Therapy of HIV 1 
A. Nature and magnitude of the HIV problem 1 
B. Rationale for ribozyme therapy; previous data 2 
C. Justification for a human trial; animal models 5 
D. Previous human gene therapy trials 6 
2. FACILITIES 7 
3. ESTIMATED DURATION OF STUDY 7 
4. SUBJECT POPULATION 8 
4.1 Inclusion Criteria 8 
4.2 Exclusion Criteria 8 
5. GENE TRANSFER PROTOCOL 9 
A. Enrollment 9 
B. Pre-treatment evaluations 1 0 
C. Gene transfer methods 1 0 
1. harvesting of lymphocytes 1 1 
2. expansion in IL-2 1 1 
3. transduction 1 1 
4. growth and selection after transduction 1 2 
5. Re-infusion 1 2 
D. Follow-up studies 1 2 
6. POTENTIAL RISKS & RISK MANAGEMENT 1 4 
6.1 Toxicity Criteria & Reporting of Adverse Effects 1 4 
6.2 Potential Risks of Gene Therapy with Ribozymes 1 4 
A. Insertional Mutagenesis 1 4 
B. Toxicity Specific to the Ribozyme 1 4 
C. Replication-competent Helper Virus 1 5 
D. Mutation of Germ Line 1 5 
E. Aminoglycoside Antibiotic Resistance 1 5 
F. Autoimmune Disease 1 6 
G. Risks Related to Harvesting and Reinfusion 1 6 
H. Confidentiality 1 6 
7. POTENTIAL BENEFITS 1 7 
8. RISK-BENEFIT RATIO 1 7 
9. EXPENSE TO SUBJECTS 17 
10. INFORMED CONSENT 1 7 
11. REFERENCES 1 8 
12. SAMPLE CONSENT 2 0 
13. APPENDIX I: DISCUSSION OF REQUIREMENT FOR AZT 2 4 
1 4. APPENDIX 1 1 : MAP & SEQUENCE OF VECTOR PMJT 2 6 
15. RESPONSE TO POINTS TO CONSIDER 2 9 
16. CURRICULA VITAE appended 
17. ATTACHED PUBLICATIONS appended 
18. IBC Approval appended 
19. IRB Approval & Investigators' Letter of Response appended 
Recombinant DNA Research, Volume 18 
[381] 
