Figure 1.

Strategies to prevent insertional mutagenesis. (a) Toward a safer vector architecture: from a long-terminal repeat (LTR)-driven vector to a self-inactivating (SIN) vector with a more physiological internal promoter. (b) Retroviral integration as a concerted action of retroviral integrase and host cell tethering factor. Integration-site preferences of murine leukemia virus (MLV)-based gammaretroviral (γRV) and HIV1-based lentiviral (LV) vectors. γRV integrations cluster with BET chromatin domains and are associated with promoter/enhancer sequences. LV vectors integrate preferentially into actively transcribed genes. BET-independent (−BET) γRV integrate less in proximity to transcriptional start sites and promoter/enhancer regions. cDNA, complementary DNA; SD/SA, splice sites; p(A), polyA site. Modified from artwork courtesy of Chris Baum.