TABLE OF COfTENTS 
Page No. 
I. Summary 6-7 
II. Background 
A. Gene Therapy 7 - 8 
B. Familial Hypercholesterolemia 
1 . Genetics 8 
2. Metabolism 8-9 
3. Clinical 9-11 
4. Level and Expression of Transferred Gene 1 2 
5. Alternative Therapies 12-14 
C. Preclinical Studies 1 4 
1 . Ex Vivo Gene Therapy in the Watanabe Heritable Hyperlipidemic Rabbit 14-16 
2. Isolation and Transduction of Human Hepatocytes 17-18 
3. Ex Vivo Gene Therapy in Nonhuman Primates 18-22 
III. Experimental Design 
A. Overall Summary 2 2-24 
B. Patient Evaluation and Selection 24-27 
C. Vectors and Viruses 
1 . Vectors for Transfer and Expression of Human LDL Receptor 2 8 
2. Description of CMV-BA-(h)LDLR Retroviral Sequences 2 9 
3. Isolation of the LDL Receptor Virus Producing Cell Line #132-10 30-34 
4. Characterization of the LDL Receptor Virus Producing Cell Line #132-10 34-35 
5. Production of the LDL Receptor Viral Supernatant 35-37 
6. Characterization of the LDL Receptor Viral Supernatant 3 7 
D. Harvest of Liver 3 7-38 
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Recombinant DNA Research, Volume 15 
