Improved functionality and potency of next generation BinMLV viral vectors toward safer gene therapy.

ABSTRACT: To develop safer retroviral murine leukemia virus (MLV)-based vectors, we previously mutated and re-engineered the MLV integrase: the W390A mutation abolished the interaction with its cellular tethering factors, BET proteins, and a retargeting peptide (the chromodomain of the CBX1 protein) was fused C-terminally. The resulting BET-independent MLV^W390A-CBX was shown to integrate efficiently and more randomly, away from typical retroviral markers. In this study, we assessed the functionality and stability of expression of the redistributed MLV^W390A-CBX vector in more depth, and evaluated safety using a clinically more relevant vector design encompassing a self-inactivated (SIN) LTR and a weak internal elongation factor 1α short (EFS) promoter. MLV^W390A-CBX-EF

SUBMITTER: Van Looveren D 

PROVIDER: S-EPMC8433069 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature