Specific insertions of zinc finger domains into Gag-Pol yield engineered retroviral vectors with selective integration properties.

ABSTRACT: Retroviral vectors offer benefits of efficient delivery and stable gene expression; however, their clinical use raises the concerns of insertional mutagenesis and potential oncogenesis due to genomic integration preferences in transcriptional start sites (TSS). We have shifted the integration preferences of retroviral vectors by generating a library of viral variants with a DNA-binding domain inserted at random positions throughout murine leukemia virus Gag-Pol, then selecting for variants that are viable and exhibit altered integration properties. We found seven permissive zinc finger domain (ZFD) insertion sites throughout Gag-Pol, including within p12, reverse transcriptase, and integrase. Comprehensive genome integration analysis showed that several ZFD insertions yielded retroviral ve

SUBMITTER: Lim KI 

PROVIDER: S-EPMC2906550 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature