ABSTRACT

I. Introduction 172

II. GAL4 Transactivating System 172

III. Tissue-Specific Promoters 176

IV. Strategies to Enhance Transcriptional Activation of Weak,

Tissue-Specific Promoters 177

V. Role of Molecular Imaging in the Noninvasive Monitoring of

Gene Expression In Vivo 181

VI. Gene Therapy Vectors 185

A. Adenoviruses 185

B. Adeno-Associated Virus 187

C. Retroviruses 187

D. Lentiviruses 187

E. Nonviral Vectors 188

VII. Imaging Pulmonary Gene Expression In Vivo 190

VIII. Transgenic Mouse Models 194

IX. Conclusion 196

References 196

I. Introduction

Selective expression of therapeutic genes in tissues of interest is an essential

requirement in gene therapy applications. This is due to the adverse effects of

therapeutic genes on normal cells during therapy. Selective targeting of cells in

patients will lead to increased treatment efficacy and safety. There are several

ways to achieve targeted expression of transgenes in cells. For instance, one

approach involves transcriptional targeting with tissue-specific regulatory

elements and enhancers. These regulatory elements may be induced to restrict

gene expression specifically to the tissue of interest.