fig2

Figure 2. Gene addition for gene therapies using retroviral vectors. Gene transduction using retroviruses such as HIV-derived lentivirus or γ-retroviruses begins when virus particles enter the cell either by endocytosis or following direct fusion of the viral envelope protein with its cognate receptor on the membrane (1,2). Upon entry, the retroviral RNA genome is released into the cytoplasm where it is reverse transcribed by a viral reverse transcriptase (3) to produce cDNA which integrates semi-randomly into the host genome using a virally expressed integrase (4). While lentiviruses can transduce dividing and non-dividing cells, simple γ-retroviruses require the disappearance of the nuclear membrane during cell division, meaning that they are only able to successfully infect dividing cell types. Integrated sequences are then expressed using the host transcriptional (5) and translational (6) machinery. Promoter sequences either in the long-terminal repeat region of the virus, or more commonly for gene therapy approaches, from a mammalian promoter sequence incorporated into the genomic cargo, are used to regulate gene expression. Created in BioRender. Torrance R (2025) https://BioRender.com/thj9v37. cDNA: Complementary DNA; HIV: human immunodeficiency virus.