Studying BET protein-chromatin occupation to understand genotoxicity of MLV-based gene therapy vectors

Abstract

Integrating retroviral vectors are used to treat genetic and acquired disorders that, theoretically, can be cured by introducing specific gene expression cassettes into patient cells. Clinical trials held over the past two decades have proven that this approach is effective in curing genetic disorders and can produce better results than the standard therapy (Touzot, F et al., 2015). Nevertheless, adverse events in a limited number of patients treated with gamma-retroviral vectors have deterred their widespread application. Specifically, vector integration occurring in proximity of proto-oncogenes resulted in insertional mutagenesis and clonal expansion of the cells (Hacein-Bey-Abina S et al., 2003).