Retrovirus Vectors in Gene Therapy: Targeting to Specific Cells

Gene transfer vectors based on retroviruses are used widely for transduction in the laboratory and they are the most commonly used vector system for the increasing number of human gene therapy trials (Morgan & Anderson 1993). Retroviral vectors are simple, they are relatively easy to produce and they possess the mechanics to enter cells efficiently and integrate the transduced gene. These attributes make them the nearest thing to an ideal gene transfer system that we have at present. However, there are several modifications that we need to make to reach the ideal system. Apart from the constant need to increase titres, there are three desirable features of a gene transfer system that are lacking in current retroviral vector systems. These are: i) the ability to infect non-dividing cells; ii) the ability to integrate the transduced gene without disruption/activation of cellular genes; iii) the ability to selectively deliver genes to specific cells and to achieve sustained expression in vivo in the desired cell type. The last of these is the topic of this article. It is a topic that is central to the future of gene therapy as it is generally agreed that gene therapy will not be widely used in medicine until genes can be delivered without the need to remove cells from the patient prior to gene transfer in vitro (Anderson 1990; Kingsman et al, 1991). Delivery in vivo is essential and, therefore, targeted viral vector delivery and selectivity is important. A second aspect of this tissue selectivity is cell specific gene expression. There is a need for simple retroviral vector systems that can achieve sustained gene expression under the control of tissue specific regulatory signals.