Inder M. Verma and Matthew D.Weitzman
Laboratory of Genetics, The Salk Institute, La Jolla, California 92037;
email: verma@salk.edu, weitzman@salk.edu
Key Words viral vectors, retrovirus/lentivirus, adenovirus, AAV, clinical trials
■ Abstract Broadly defined, the concept of gene therapy involves the transfer of genetic material into a cell, tissue, or whole organ, with the goal of curing a disease or at least improving the clinical status of a patient. A key factor in the success of gene therapy is the development of delivery systems that are capable of efficient gene transfer in a variety of tissues, without causing any associated pathogenic effects. Vectors based upon many different viral systems, including retroviruses, lentiviruses, adenoviruses,and adeno-associated viruses, currently offer the best choice for efficient gene delivery.Their performance and pathogenicity has been evaluated in animal models, and encouraging
results form the basis for clinical trials to treat genetic disorders and acquired diseases. Despite some initial success in these trials, vector development remains a seminal concern for improved gene therapy technologies.

CONTENTS
INTRODUCTION . . 711
VIRAL VECTORS . . 713
RNA VIRUS VECTORS 714
Retroviruses . . 714
DNA VIRUS VECTORS 719
Adenovirus 719
Adeno-Associated Virus . . 721
Herpesvirus 723
VECTOR TROPISM AND THE SPECIFICITY OF TRANSDUCTION . 725
VECTOR RECOGNITION, PROCESSING, AND INTEGRATION . . 727
Gene Regulation . . 728
CLINICAL TRIALS: SUCCESSES AND SETBACKS 729
PERSPECTIVES: WHAT IS NEXT? . . 732