HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
TABLE OF CONTENTS 
Page 
I . SUMMARY 8 
II. SPECIFIC AIMS 10 
III. SCIENTIFIC AND TECHNICAL BACKGROUND 11 
A. The state of the art in hepatic transplantation. 11 
B. The rationale for hepatocellular transplantation. 12 
C. Hepatocellular harvest, cultivation, and transplantation. 13 
D. The potential for rejection of hepatocellular grafts. 16 
E. Rationale for use of a marker gene in transplanted hepatocytes. 16 
F. Retroviral mediated gene transfer and somatic gene therapy. 18 
G. The liver as a target for somatic gene therapy. 21 
H. Transduction off hepatocytes with recombinant retroviral vectors 
and expression of recombinant genes. 22 
I. Issues in proposing gene transfer in human subjects. 25 
J. Precedents and implications of the present work. 25 
K. Clinical considerations in gene transfer in human subjects. 27 
L. The balance of risk and benefit - components of informed consent 30 
IV. EXPERIMENTAL DESIGN 32 
A. Patient evaluation and selection. 32 
B. Harvest and cultivation of hepatocytes. 35 
C. Surgical approaches to the delivery of hepatocytes. 39 
D. Transduction of hepatocytes. 41 
E. Evaluation of engraftment. 44 
F. Evaluation of rejection. 47 
G. Surveillance for adverse consequences of retroviral gene 
transfer. 48 
H. Long-term follow-up. 49 
V. REFERENCES CITED 51 
VI. OSHA STATEMENT 56 
VII. INFORMED CONSENT 56 
VIII. SPECIFIC RESPONSES TO "POINTS TO CONSIDER..." 61 
IX. SUBMISSION FOR IRB REVIEW AT BAYLOR COLLEGE OF MEDICINE AND 
TEXAS CHILDREN'S HOSPITAL 81 
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Recombinant DNA Research, Volume 14 
