Project Description

Therapeutic efficacy of gamma-retrovirus-mediated gene therapy was marred by insertional mutagenesis because of their integration site preference in close proximity to transcription start sites of known proto-oncogenes as well as tumor suppressor genes leading to their activation and inactivation, respectively. This was attributed to the strong viral LTR promoter/enhancer activity of the MoMLV-based gamma-retroviral vectors that were used in the early clinical trials. Recently, cases of clonal expansion have been reported with the use of LV vectors for the treatment of β-thalassemia via transcriptional activation of HMGA2 gene in erythroid cells. Therefore, retargeting LV integrations to safer locations within the genome using an artificial tethering factor could have great implications for their use in future gene therapy clinical trials.