Abstract
During HIV-1 reverse transcription, central initiation of the plus-strand DNA at the central polypurine tract (cPPT) and central termination at the central termination sequence (CTS) lead to the formation of a three-stranded DNA structure: the HIV-1 central DNA flap. We recently reported that the DNA flap acts as a cis-active determinant of HIV-1 genome nuclear import. Commonly employed HIV-1–derived vectors (HR vectors) lack the central DNA flap. Here we report that the insertion of this DNA flap sequence into HR vectors (TRIP vectors) improves gene transduction in neural cells, ex vivo and in vivo, in rat brain. When neural cells are exposed to increasing concentrations of TRIP vector particles, transgene expression correlates with the dose of vector. This effect contrasts with the plateau observed when using an HR vector. We further demonstrate that the increase of in vivo transduction efficiency obtained with TRIP vectors is due to the stimulation of their genome nuclear import.
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Acknowledgements
We thank N. Taylor for critical reading of the manuscript, D. De Saint-Jan for the rESE, and F. Lachapelle for his kind assistance. V.Z. was supported by a fellowship from Association Française contre les Myopathies and C.Se. from Vaincre les Maladies Lysosomales. This work was supported by grants from Agence Nationale pour la Recherche contre le SIDA and Association Française contre les Myopathies.
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Zennou, V., Serguera, C., Sarkis, C. et al. The HIV-1 DNA flap stimulates HIV vector-mediated cell transduction in the brain. Nat Biotechnol 19, 446–450 (2001). https://doi.org/10.1038/88115
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DOI: https://doi.org/10.1038/88115
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