Development of Safer Gene Delivery Systems to Minimize the Risk of Insertional Mutagenesis-Related Malignancies: A Critical Issue for the Field of Gene Therapy

Figure 4

This figure illustrates the replication cycle of the genera of retroviridae. As shown at the top of the figure, the proviral DNA transcribes the retroviral mRNA, which is then packaged into the virion. The retroviral mRNA contains only one copy of the U3 and U5 regions. After the virus enters the target cells, the retroviral mRNA is released in the cellular cytoplasm and reverse transcribed. During this process, the U3 region present at the 3′-end of the retroviral mRNA is duplicated at the 5′-end of the newly synthesized proviral DNA, whereas the U5 region in the 5′-end of the retroviral mRNA is copied at the 3′-end of the proviral DNA. The proviral DNA associates with other retroviral and cellular factors to form the preintegration complex, which can cross the nuclear membrane and integrate into the infected cell’s genome.