Cell and Tissue Gene Targeting with Lentiviral Vectors

One of the main advantages of using lentivectors is their capacity to transduce a wide range of cell types, independently from the cell cycle stage. However, transgene expression in certain cell types is sometimes not desirable, either because of toxicity, cell transformation, or induction of transgene-specific immune responses. In other cases, specific targeting of only cancerous cells within a tumor is sought after for the delivery of suicide genes. Consequently, great effort has been invested in developing strategies to control transgene delivery/expression in a cell/tissue-specific manner. These strategies can broadly be divided in three; particle pseudotyping (surface targeting), which entails modification of the envelope glycoprotein (ENV); transcriptional targeting, which utilizes cell-specific promoters and/or inducible promoters; and posttranscriptional targeting, recently applied in lentivectors by introducing sequence targets for cell-specific microRNAs. In this chapter we describe each of these strategies providing some illustrative examples.