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Abrogated cryptic activation of lentiviral transfer vectors.


ABSTRACT: Despite significant improvements in lentivirus (LV) vector-based gene therapy there are still several safety risks using LV vectors including the potential formation of replication-competent LV particles. To address this shortcoming, we constructed a novel and safer gene transfer system using modified SIN-based LV gene transfer vectors. Central to our approach is a conditional deletion of the ? packaging signal after integration in the target genome. Here we demonstrate that after transduction of target cells, conventional SIN-based LV transfer vectors can still be mobilized. However mobilization is rendered undetectable if transductions are followed by a Cre/loxP-mediated excision of ?. Thus conditional elimination of the packaging signal may represent another advance in increasing the safety of LV vectors for gene therapeutic treatment of chronic diseases.

SUBMITTER: Luche RM 

PROVIDER: S-EPMC3365281 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Abrogated cryptic activation of lentiviral transfer vectors.

Luche Ralf M RM   Enssle Joerg J   Kiem Hans-Peter HP  

Scientific reports 20120601


Despite significant improvements in lentivirus (LV) vector-based gene therapy there are still several safety risks using LV vectors including the potential formation of replication-competent LV particles. To address this shortcoming, we constructed a novel and safer gene transfer system using modified SIN-based LV gene transfer vectors. Central to our approach is a conditional deletion of the Ψ packaging signal after integration in the target genome. Here we demonstrate that after transduction o  ...[more]

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