Locus control region of the human CD2 gene in a lentivirus vector confers position-independent transgene expression

Journal of Virology
C M KowolikJ K Yee

Abstract

Vectors derived from murine leukemia virus (MLV) have been used in many human gene therapy clinical trials. However, insertion of the locus control regions (LCRs) derived from the beta-globin gene locus or the CD2 gene into MLV vectors frequently led to vector rearrangement. Since the human immunodeficiency virus (HIV) sequence diverges significantly from the MLV sequence, we tested whether the LCR sequence is more stable in the context of an HIV vector. Clones derived from human fibrosarcoma line HT1080 cells transduced with an HIV vector containing the T-cell-specific CD2 LCR exhibit the same wide range of transgene expression as clones lacking the LCR. In contrast, Jurkat and primary T-cell clones derived from the transduction of the LCR-containing vector show, on average, a three- to fourfold increase in transgene expression relative to that of the control vector. This is consistent with previous observations that the CD2 LCR contains a T-cell-specific enhancer. In addition, the clones derived from the LCR-containing vector have a much lower clonal variation in transgene expression than those derived from the control vector. We also demonstrate that the level of transgene expression is proportional to the vector copy number...Continue Reading

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Citations

Dec 3, 2002·Current Opinion in Biotechnology·Aaron C LoganDonald B Kohn
Jan 18, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Alex H Chang, Michel Sadelain
Aug 12, 2003·Human Gene Therapy·Boris EngelsWolfgang Uckert
Mar 23, 2013·Human Gene Therapy·Michael N AntoniouOmer Anakok
Jun 19, 2007·American Journal of Respiratory Cell and Molecular Biology·Benjamin HendricksonCarolyn Lutzko
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Apr 12, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Priscilla Y YamJiing-Kuan Yee

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