Retroviruses in Human Gene Therapy

Abstract

Abstract A retrovirus‐based gene transfer system consists of two components: the transfer vector, which harbours a foreign gene linked to elements needed for retroviral replication, and the packaging cell, which supplies the necessary retroviral proteins for transfer of the vector through a single round of viral replication. A hallmark of retroviral replication is the stable maintenance of the transferred gene(s) during cell division. The first type of transfer vectors used in gene therapy trials were derived from mouse retroviruses and referred to as retroviral vectors. Lentiviral vectors are derived from human immunodeficiency virus type 1 and exhibit distinct features that provide advantages in some settings. Retroviral and lentiviral vectors are being used in clinical trials for several diseases, including monogenic diseases and cancer. The clinical protocols include gene transfer in vivo as well as ex vivo , the latter being followed by installation of the genetically modified cells into the body. Key Concepts: The retroviral replication machinery leads to stable maintenance of a transferred gene. The stable integration of retroviral vectors into a chromosome of the target cell may have adverse effects on neighbouring genes. Retroviral gene transfer does not require the expression of retroviral genes in the target cell. The term retroviral vector is used for a vector based on murine leukaemia virus. The term lentiviral vector is used for a vector based on human immunodeficiency virus type 1. Retroviral vectors allow gene transfer only to dividing cells, whereas lentiviral vectors target dividing as well as nondividing cells. In clinical protocols using retroviral or lentiviral vectors, gene transfer may take place ex vivo or in vivo . The selectivity of retroviral vectors for dividing cells has been exploited to target tumour cells.