Chapter 14. Genetic Engineering of Targeted Retroviral Vectors

  1. David T. Curiel M.D. and
  2. Joanne T. Douglas Ph.D.
  1. Erlinda M. Gordon M.D.1,
  2. Frederick L. Hall Ph.D.2,
  3. Robert W. Beart Jr. M.D.3 and
  4. W. French Anderson M.D.4

Published Online: 31 MAR 2003

DOI: 10.1002/0471234303.ch14

Vector Targeting for Therapeutic Gene Delivery

Vector Targeting for Therapeutic Gene Delivery

How to Cite

Gordon, E. M., Hall, F. L., Beart, R. W. and Anderson, W. F. (2002) Genetic Engineering of Targeted Retroviral Vectors, in Vector Targeting for Therapeutic Gene Delivery (eds D. T. Curiel and J. T. Douglas), John Wiley & Sons, Inc., Hoboken, NJ, USA. doi: 10.1002/0471234303.ch14

Editor Information

  1. Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, The University of Alabama at Birmingham, USA

Author Information

  1. 1

    Gene Therapy Laboratories and the Department of Pediatrics, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA

  2. 2

    Gene Therapy Laboratories and the Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA

  3. 3

    The Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA

  4. 4

    Gene Therapy Laboratories and the departments of Surgery and Biochemistry, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA

Publication History

  1. Published Online: 31 MAR 2003
  2. Published Print: 9 AUG 2002

ISBN Information

Print ISBN: 9780471434795

Online ISBN: 9780471234302

SEARCH

Keywords:

  • targeted injectable retroviral vectors;
  • MuLV envelope proteins;
  • lesion-targeting;
  • cell cycle control;
  • cancer gene therapy

Summary

At the turn of the century, gene therapy remains poised at the threshold of modernizing medicine. While holding great promise for the treatment of numerous diseases, the field of gene therapy has been disappointingly slow in the development of safe and efficient gene delivery systems (Anderson, 1998). In recent years, we developed a targeting strategy that now enables gene therapy vectors to target “areas of pathology” within the body. Taking advantage of the physiologic surveillance function present in a discrete collagen-binding domain of coagulation von Willebrand factor (vWF), we incorporated these coding sequences into the primary structure of the murine leukemia virus (MuLV) 4070A amphotropic envelope protein. The resultant matrix-targeted vector exhibited a lesion-seeking feature, i.e., the ability to accumulate at sites of exposed collagen within the lesions that are created by growing tumors or vascular neointima. In this chapter, we will discuss the evolution of various retroviral vector targeting strategies in our laboratories, with particular emphasis on the clinical potential of this lesion-seeking injectable vector system in the treatment of metastatic cancer, balloon angioplasty/stent injury-induced vascular restenosis and post-Excimer laser corneal haze.