| 초록 |
Retroviral vectors show long‐term gene expression in gene therapy through integration into the human genome. Murine leukemia virus (MLV) is used as a representative retroviral vector. However, frequent integrations of MLV vectors into transcriptional start sites (TSSs) can lead to activation of oncogenes. Therefore, the MLV integration preference for TSSs limits its wider use in clinical applications. To reduce the integration preference of MLV vectors, we perturbed the structure of the viral integrase that determines integration sites. For this goal, we inserted zinc fingers, histones and leucine zippers, having DNA‐binding property, into internal sites of MLV integrase. This integrase engineering yielded multiple vectors that showed significantly different integration patterns compared to that of wildtype vector. Some mutant vectors did not prefer the key regulatory genomic domains, TSSs. Moreover, a few vectors did not integrate into the genomic sites near the TSSs of oncogenes. |
