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Báo cáo sinh học: " Influence of insulators on transgene expression from integrating and non-integrating lentiviral vectors"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Influence of insulators on transgene expression from integrating and non-integrating lentiviral vectors | Grandchamp et al. Genetic Vaccines and Therapy 2011 9 1 http www.gvt-journal.eom content 9 1 1 z GENETIC VACCINES AND THERAPY RESEARCH Open Access Influence of insulators on transgene expression from integrating and non-integrating lentiviral vectors 1.2 12 13 1.4 1.2 Nicolas Grandchamp Dorothée Henriot Stephanie Philippe Lahouari Amar Suzanna Ursulet Che Serguera1 5 Jacques Mallet1 Chamsy Sarkis1 2 Abstract Background The efficacy and biosafety of lentiviral gene transfer is influenced by the design of the vector. To this end properties of lentiviral vectors can be modified by using cis-acting elements such as the modification of the U3 region of the LTR the incorporation of the central flap cPPT-CTS element or post-transcriptional regulatory elements such as the woodchuck post-transcriptional regulatory element WPRE . Recently several studies evaluated the influence of the incorporation of insulators into the integrating lentiviral vector genome on transgene expression level and position effects. Methods In the present study the influence of the matrix attachment region MAR of the mouse immunoglobulin-K Ig-ft or the chicken lysozyme ChL gene was studied on three types of HIV-1-derived lentiviral vectors selfinactivating SIN lentiviral vectors LV double-copy lentiviral vectors DC and non-integrating lentiviral vectors NILVs in different cell types HeLa HEK293T NIH-3T3 Raji and T Jurkat cell lines and primary neural progenitors. Results and Discussion Our results demonstrate that the Ig-K MAR in the context of LV slightly increases transduction efficiency only in Hela NIH-3T3 and Jurkat cells. In the context of double-copy lentiviral vectors the Ig-K MAR has no effect or even negatively influences transduction efficiency. In the same way in the context of non-integrating lentiviral vectors the Ig-K MAR has no effect or even negatively influences transduction efficiency except in differentiated primary neural progenitor cells. The ChL MAR in the context of .