Chapter 14. Genetic Engineering of Targeted Retroviral Vectors
- David T. Curiel M.D.,
- Joanne T. Douglas Ph.D.
Published Online: 31 MAR 2003
Copyright © 2002 John Wiley & Sons, Inc.
Vector Targeting for Therapeutic Gene Delivery
How to Cite
Gordon, E. M., Hall, F. L., Beart, R. W. and Anderson, W. F. (2003) 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
Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, The University of Alabama at Birmingham, USA
- Published Online: 31 MAR 2003
- Published Print: 9 AUG 2002
Print ISBN: 9780471434795
Online ISBN: 9780471234302
- targeted injectable retroviral vectors;
- MuLV envelope proteins;
- cell cycle control;
- cancer gene therapy
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.