3 Lentiviral Vectors

Abstract

Somatic gene therapy requires the efficient delivery and sustained expression of a therapeutic gene into the tissues of a human body. Such an approach has tremendous therapeutic potential for several inherited and acquired diseases. However, major obstacles must be overcome to fulfill these high expectations. Among them, the development of more effective gene delivery systems is widely viewed as a critical challenge to gene therapy investigators (Verma and Somia 1997).

Retroviral vectors have long been favored as a gene transfer tool for several reasons. First, they integrate efficiently into the genome of the target cell. Second, they do not transfer any viral gene, thus alleviating the risk of immune response against the transduced cells. Both of these properties are likely to be crucial for achieving sustained expression of the transgene. Third, the genome and the life cycle of retroviruses are relatively simple and well studied, which has allowed a continuous improvement in the vector design and the generation of stable producer systems amenable to characterization and scaleup. Fourth, retroviral vectors can transfer a sizeable amount of DNA, up to 7.0 kb of foreign genetic material (Miller et al. 1993).

Until now, the retroviral vectors used in clinical trials have been derived from onco-retroviruses such as the Moloney murine leukemia virus (MLV). A major drawback of these vectors is that they can only transduce cells that divide shortly after infection (Miller et al. 1990). While actively dividing cells are found in several body tissues, they are short-lived and continuously replaced. The...