Injectable retroviral particles for human gene therapy

• Published in: Advanced drug delivery reviews 1995-12, Vol.17 (3), p.213-226
• Main Authors: Squinto, Stephen P., Rollins, Scott A., Springhorn, Jeremy P., Fodor, William L., Rother, Russell P.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biotechnology; Fundamental and applied biological sciences. Psychology; Gene therapy; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/0169-409X(95)00054-B

The use of retroviral-mediated gene transfer as an in vivo approach for the treatment of human disease has been limited by the inability of retroviral vectors to survive the host humoral immune system. The rapid inactivation of retroviruses that ensues following exposure to human or primate serum has been largely attributed to the activition of the complement cascade mediated through the classical pathway. We have extensively investigated and experimentally defined the relationship between the human complement cascade and retroviral vector particle inactivation. These research efforts have allowed us to develop several related solutions to the problems of retroviral inactivation by human complement. Furthermore, the approaches we describe here establish commercially viable methods to prevent complement-mediated inactivation of retroviral vector particles and producer cells in human blood which should enable and expedite the direct in vivo retroviral-mediated gene transfer in humans.