Enhanced transgene expression in cord blood CD34(+)-derived hematopoietic cells, including developing T cells and NOD/SCID mouse repopulating cells, following transduction with modified trip lentiviral vectors

Molecular Therapy : the Journal of the American Society of Gene Therapy
A SirvenA Dubart-Kupperschmitt

Abstract

The recent development of lentivirus-derived vectors is an important breakthrough in gene transfer technology because these vectors allow transduction of nondividing cells such as hematopoietic stem cells (HSC), due to an active nuclear import of reverse-transcribed vector DNA. We recently demonstrated that addition of the central DNA flap of HIV-1 to an HIV-derived lentiviral vector strikingly increases transduction of CD34(+) cells. We now describe improvements of the transduction protocol designed to preserve HSC properties and two modifications of the previously described TRIP-CMV vector. First, deletion of the enhancer/promoter of the 3' LTR in the TRIP-CMV vector resulted in a safer vector (TRIPDeltaU3-CMV) with conserved transduction efficiency and increased EGFP transgene expression. Second, the original internal CMV promoter was replaced with the promoter for the ubiquitously expressed elongation factor 1alpha (EF1alpha). This promoter substitution resulted in a significantly more homogeneous expression of the EGFP transgene in all hematopoietic cell types, including CD34(+)-derived T lymphocytes, in which the CMV promoter was inactive, and NOD/SCID mouse repopulating cells. We thus present here an HIV-derived lentivir...Continue Reading

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Citations

Sep 18, 2007·Molecular Biotechnology·Adam S Cockrell, Tal Kafri
Jun 19, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Fatine BenjellounMarina Cavazzana-Calvo
Dec 14, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Elodie Robert-RichardFrançois Moreau-Gaudry
Jan 18, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Alex H Chang, Michel Sadelain
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Oct 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Benjamin B LandCharles Chavkin
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Oct 1, 2005·Blood·Aurélie KieusseianAnne Dubart-Kupperschmitt
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