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Publication Detail
Stable Gene Transfer to Muscle Using Non-integrating Lentiviral Vectors
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Apolonia L, Waddington SN, Fernandes C, Ward NJ, Bouma G, Blundell MP, Thrasher AJ, Collins MK, Philpott NJ
  • Publication date:
    14/08/2007
  • Journal:
    Mol Ther.
  • Keywords:
    lentiviral vectors, gene transfer, A, all, AND, ARTICLE, Cells, Child, FOR, Health, Human, JOURNAL, London, OF, pathology, THE, therapy, Universities
  • Addresses:
    [1] 1Molecular Immunology Unit, Institute of Child Health, London, UK [2] 2Great Ormond Street for Hospital NHS Trust, London, UK [3] 3Department of Immunology and Molecular Pathology, Windeyer Institute, University College London, UK
  • Notes:
    DA - 20070816IS - 1525-0016 (Print)LA - ENGPT - JOURNAL ARTICLE
Abstract
Human immunodeficiency virus (HIV)-based lentiviral vectors (LVs) hold immense promise for gene delivery applications because of their relatively large packaging capacity and their ability to infect a range of cell types. The genome of HIV non-specifically integrates into the host genome, and this promotes efficient, stable transgene expression in dividing cells. However, integration can also be problematic because of variations in gene expression among cells, possible gene silencing and, most importantly, insertional mutagenesis which can lead to undesirable effects such as malignant transformation. In order to alleviate these problems, we have developed a range of non-integrating LVs (NILVs) by introducing point mutations into the catalytic site, chromosome binding site, and viral DNA binding site of the viral integrase (IN). In addition, we have mutated the IN attachment (att) sites within the HIV long terminal repeats (LTRs). All of the vectors produced show efficient reverse transcription and transgene expression in dividing cells and prolonged expression in non-dividing myotubes. Finally, we show that NILV can be used for achieving highly effective gene transfer and expression in muscle in vivo.Molecular Therapy (2007) doi:10.1038/sj.mt.6300281
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