Retroviral Vectors in Gene Therapy: Mechanism of Integration, Successes in Gene Therapy Trials, Emerging Problems and Potential Solutions

Retroviral vectors have gained an increasing value in gene therapy because they stably deliver therapeutic genes to the host cell genome. These therapeutic genes are supposed to rectify consequences of inherited and acquired mutated genes in the host cell genome, or alter host cell function to cure diseases. In the following section we will discuss the biology and life cycle of retroviruses which starts with viral entry into the host cell, reverse transcription of viral RNA, nuclear import of the provirus, and finally integration of viral DNA into the cell host genome (Flint, Racaniello et al. 2004). Integration involves viral and host cellular proteins. Their role is discussed in the third and fourth sections of this chapter. Recently, the process of integration site selection (which is where the viral DNA integrates with the host cell DNA) has been quite understood throughout many in vitro and in vivo studies. The human genome project has enabled us to identify integration site preferences for retroviral vectors in human trials. The results of these human trials are reviewed in the fifth section of the chapter. Finally, the last section of the chapter will demonstrate the latest gene therapy trials attempts to control integration sites by manipulation of retrovirus genes and proteins.