Generation of retroviral packaging and producer cell lines for large-scale vector production with improved safety and titer.

Abstract

Retroviral vectors based on Moloney Murine Leukemia Virus (MLV), described more than 15 years ago (), first entered clinical trials in 1990 (). Since then, a greater understanding of the basic retrovirus biology and how it relates to the production of recombinant retroviral vectors has helped overcome some of the initial hurdles, including low titer, outbreak of replication-competent retrovirus (RCR), and complement inactivation of vector (, , , ). Subsequently, retroviral vectors have become a very safe and powerful tool for efficient in vitro, ex vivo, and in vivo gene transfer for proliferating cells. Several refinements in recombinant MLV vector technology were necessary, particularly for clinical trials using systemic administration of very high vector doses (>1010 transducing units), thus necessitating efficient large-scale manufacture of safe and high-titer retroviral vector preparations.