Retroviral Vectors for Suicide Gene Therapy

A recombinant retroviral vector is one of many available options for effecting gene transfer. To date, this type of vector has been most widely used and is involved in more than a third of current gene therapy trials, many of which are for delivery of suicide genes in the context of cancer treatment (1 ). Many issues that may impinge upon the choice of vector are specific to individual applications. However, in general, retroviral vectors may be chosen for reasons of their relatively high efficiency of gene delivery, the stable integration of the transgene delivered, and their immunological “silence.” A distinction exists between vectors based on murine leukemia virus (MLV) and those derived from lentiviruses, such as human immunodeficiency virus (HIV). MLV vector gene delivery is restricted to proliferating target cells (2 ), resulting from a requirement for breakdown of the nuclear membrane, whereas HIV vectors can additionally infect nondividing cells. Lentiviral vectors are in their relative infancy and will not be considered further in this chapter. Depending on the proposed application, it will be necessary to consider whether this proliferation requirement for MLV vectors is advantageous or not. Efficacy shown by several of the suicide enzyme/prodrug systems, such as HSV thymidine kinase (HSV-TK) and gancyclovir, is similarly dependent on cell proliferation.