Gene therapy viruses and vectors. The genome of both wild-type murine MLV (A) and the HIV-1 virus and the gene therapy vectors derived from them (B). The initial retroviral vectors had full-length long terminal repeats (LTRs) with intact U3 region (which carries the viral enhancer and promoter). With the current generation of LVs, the U3 region of the 3′ LTR is deleted and in the 5′ LTR, it is replaced by a CMV promoter in the 5′ LTR. The CMV promoter is only used in packaging the vector and is not transmitted to host cells. The HIV envelope is replaced by the VSV-G envelope. (C) Prototypic globin LV vector. Reprinted with permission from Chandrakasan and Malik, 2014.²⁵