Retargeted Foamy Virus Vectors Integrate Less Frequently Near Proto-oncogenes.

ABSTRACT: Retroviral gene therapy offers immense potential to treat many genetic diseases and has already shown efficacy in clinical trials. However, retroviral vector mediated genotoxicity remains a major challenge and clinically relevant approaches to reduce integration near genes and proto-oncogenes are needed. Foamy retroviral vectors have several advantages over gammaretroviral and lentiviral vectors including a potentially safer integration profile and a lower propensity to activate nearby genes. Here we successfully retargeted foamy retroviral vectors away from genes and into satellite regions enriched for trimethylated histone H3 at lysine 9 by modifying the foamy virus Gag and Pol proteins. Retargeted foamy retroviral vectors integrated near genes and proto-oncogenes less often (p < 0.001)

SUBMITTER: Hocum JD 

PROVIDER: S-EPMC5095648 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature