SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sirven, A. Articles by Charneau, P. Search for Related Content PubMed PubMed Citation Articles by Sirven, A. Articles by Charneau, P. Related Collections Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2000, Vol. 96, No. 13, pp. 4103-4110 GENE THERAPY The human immunodeficiency virus type-1 central DNA flap is a crucial determinant for lentiviral vector nuclear import and gene transduction of human hematopoietic stem cells Aude Sirven, Françoise Pflumio, Véronique Zennou, Monique Titeux, William Vainchenker, Laure Coulombel, Anne Dubart-Kupperschmitt, and Pierre Charneau From the Institut National de la Santé et de la Recherche Médicale (INSERM) U362, Institut Gustave Roussy, Villejuif, France, and the Unité d'Oncologie Virale, Institut Pasteur, Paris, France. Gene transfer in human hematopoietic stem cells (HSCs) has great potential for both gene therapy and the understanding of hematopoiesis. As HSCs have extensive proliferative capacities, stable gene transfer should include genomic integration of the transgene. Lentiviral vectors are now preferred to oncoretroviral vectors especially because they integrate in nondividing cells such as HSCs, thereby avoiding the use of prolonged cytokine stimulation. Human immunodeficiency virus type-1 (HIV-1) has evolved a complex reverse transcription strategy including a central strand displacement event controlled in cis by the central polypurine tract (cPPT) and the central termination sequence (CTS). This creates, at the center of HIV-1 linear DNA molecules, a 99-nucleotide-long plus-strand overlap, the DNA flap, which acts as a cis-determinant of HIV-1 genome nuclear import. The reinsertion of the DNA flap sequence in an HIV-derived lentiviral vector promotes a striking increase of gene transduction efficiency in human CD34+ hematopoietic cells, and the complementation of the nuclear import defect present in the parental vector accounts for this result. In a short ex vivo protocol, the flap-containing vector allows efficient transduction of the whole hierarchy of human HSCs including both slow-dividing or nondividing HSCs that have multiple lymphoid and myeloid potentials and primitive cells with long-term engraftment ability in nonobese diabetic/severe combined immunodeficiency mice (NOD/SCID). © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Wang, D. Li, T. A. Dawson, and D. J. Paterson Long-term effect of neuronal nitric oxide synthase over-expression on cardiac neurotransmission mediated by a lentiviral vector J. Physiol., July 15, 2009; 587(14): 3629 - 3637. [Abstract] [Full Text] [PDF] F. Armstrong, P. B. de la Grange, B. Gerby, M.-C. Rouyez, J. Calvo, M. Fontenay, N. Boissel, H. Dombret, A. Baruchel, J. Landman-Parker, et al. NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity Blood, February 19, 2009; 113(8): 1730 - 1740. [Abstract] [Full Text] [PDF] M. Alonso, I. Ortega-Perez, M. S. Grubb, J.-P. Bourgeois, P. Charneau, and P.-M. Lledo Turning Astrocytes from the Rostral Migratory Stream into Neurons: A Role for the Olfactory Sensory Organ J. Neurosci., October 22, 2008; 28(43): 11089 - 11102. [Abstract] [Full Text] [PDF] Z. Ao, G. Huang, H. Yao, Z. Xu, M. Labine, A. W. Cochrane, and X. Yao Interaction of Human Immunodeficiency Virus Type 1 Integrase with Cellular Nuclear Import Receptor Importin 7 and Its Impact on Viral Replication J. Biol. Chem., May 4, 2007; 282(18): 13456 - 13467. [Abstract] [Full Text] [PDF] D. C. Thomas, Y. A. Voronin, G. N. Nikolenko, J. Chen, W.-S. Hu, and V. K. Pathak Determination of the Ex Vivo Rates of Human Immunodeficiency Virus Type 1 Reverse Transcription by Using Novel Strand-Specific Amplification Analysis J. Virol., May 1, 2007; 81(9): 4798 - 4807. [Abstract] [Full Text] [PDF] H. Ly, Y. Kawase, R. Yoneyama, and R. J. Hajjar Gene Therapy in the Treatment of Heart Failure Physiology, April 1, 2007; 22(2): 81 - 96. [Abstract] [Full Text] [PDF] D. J. Garfinkel, K. M. Stefanisko, K. M. Nyswaner, S. P. Moore, J. Oh, and S. H. Hughes Retrotransposon Suicide: Formation of Ty1 Circles and Autointegration via a Central DNA Flap J. Virol., December 15, 2006; 80(24): 11920 - 11934. [Abstract] [Full Text] [PDF] N. Arhel, S. Munier, P. Souque, K. Mollier, and P. Charneau Nuclear import defect of human immunodeficiency virus type 1 DNA flap mutants is not dependent on the viral strain or target cell type. J. Virol., October 1, 2006; 80(20): 10262 - 10269. [Abstract] [Full Text] [PDF] S. Wurtzer, A. Goubard, F. Mammano, S. Saragosti, D. Lecossier, A. J. Hance, and F. Clavel Functional Central Polypurine Tract Provides Downstream Protection of the Human Immunodeficiency Virus Type 1 Genome from Editing by APOBEC3G and APOBEC3B. J. Virol., April 1, 2006; 80(7): 3679 - 3683. [Abstract] [Full Text] [PDF] E. MORDELET, K. KISSA, A. CRESSANT, F. GRAY, S. OZDEN, C. VIDAL, P. CHARNEAU, and S. GRANON Histopathological and cognitive defects induced by Nef in the brain FASEB J, December 1, 2004; 18(15): 1851 - 1861. [Abstract] [Full Text] [PDF] Y. Soda, K. Tani, Y. Bai, M. Saiki, M. Chen, K. Izawa, S. Kobayashi, S. Takahashi, K. Uchimaru, T. Kuwabara, et al. A novel maxizyme vector targeting a bcr-abl fusion gene induced specific cell death in Philadelphia chromosome-positive acute lymphoblastic leukemia Blood, July 15, 2004; 104(2): 356 - 363. [Abstract] [Full Text] [PDF] B. M. Davis, L. Humeau, V. Slepushkin, G. Binder, L. Korshalla, Y. Ni, E. O. Ogunjimi, L.-F. Chang, X. Lu, and B. Dropulic ABC transporter inhibitors that are substrates enhance lentiviral vector transduction into primitive hematopoietic progenitor cells Blood, July 15, 2004; 104(2): 364 - 373. [Abstract] [Full Text] [PDF] Y. A. Voronin and V. K. Pathak Frequent Dual Initiation in Human Immunodeficiency Virus-Based Vectors Containing Two Primer-Binding Sites: a Quantitative In Vivo Assay for Function of Initiation Complexes J. Virol., May 15, 2004; 78(10): 5402 - 5413. [Abstract] [Full Text] [PDF] E. Ravet, D. Reynaud, M. Titeux, B. Izac, S. Fichelson, P.-H. Romeo, A. Dubart-Kupperschmitt, and F. Pflumio Characterization of DNA-binding-dependent and -independent functions of SCL/TAL1 during human erythropoiesis Blood, May 1, 2004; 103(9): 3326 - 3335. [Abstract] [Full Text] [PDF] Z. Ao, X. Yao, and E. A. Cohen Assessment of the Role of the Central DNA Flap in Human Immunodeficiency Virus Type 1 Replication by Using a Single-Cycle Replication System J. Virol., March 15, 2004; 78(6): 3170 - 3177. [Abstract] [Full Text] [PDF] C. Goujon, L. Jarrosson-Wuilleme, J. Bernaud, D. Rigal, J.-L. Darlix, and A. Cimarelli Heterologous Human Immunodeficiency Virus Type 1 Lentiviral Vectors Packaging a Simian Immunodeficiency Virus-Derived Genome Display a Specific Postentry Transduction Defect in Dendritic Cells J. Virol., September 1, 2003; 77(17): 9295 - 9304. [Abstract] [Full Text] [PDF] J. C. Segovia, G. Guenechea, J. M. Gallego, J. M. Almendral, and J. A. Bueren Parvovirus Infection Suppresses Long-Term Repopulating Hematopoietic Stem Cells J. Virol., August 1, 2003; 77(15): 8495 - 8503. [Abstract] [Full Text] [PDF] R. V. Parry, C. A. Rumbley, L. H. Vandenberghe, C. H. June, and J. L. Riley CD28 and Inducible Costimulatory Protein Src Homology 2 Binding Domains Show Distinct Regulation of Phosphatidylinositol 3-Kinase, Bcl-xL, and IL-2 Expression in Primary Human CD4 T Lymphocytes J. Immunol., July 1, 2003; 171(1): 166 - 174. [Abstract] [Full Text] [PDF] W. Piacibello, S. Bruno, F. Sanavio, S. Droetto, M. Gunetti, L. Ailles, F. S. de Sio, A. Viale, L. Gammaitoni, A. Lombardo, et al. Lentiviral gene transfer and ex vivo expansion of human primitive stem cells capable of primary, secondary, and tertiary multilineage repopulation in NOD/SCID mice Blood, December 15, 2002; 100(13): 4391 - 4400. [Abstract] [Full Text] [PDF] S. Lyonnais, C. Hounsou, M.-P. Teulade-Fichou, J. Jeusset, E. L. Cam, and G. Mirambeau G-quartets assembly within a G-rich DNA flap. A possible event at the center of the HIV-1 genome Nucleic Acids Res., December 1, 2002; 30(23): 5276 - 5283. [Abstract] [Full Text] [PDF] A. Limon, N. Nakajima, R. Lu, H. Z. Ghory, and A. Engelman Wild-Type Levels of Nuclear Localization and Human Immunodeficiency Virus Type 1 Replication in the Absence of the Central DNA Flap J. Virol., October 25, 2002; 76(23): 12078 - 12086. [Abstract] [Full Text] [PDF] J. D. Dvorin, P. Bell, G. G. Maul, M. Yamashita, M. Emerman, and M. H. Malim Reassessment of the Roles of Integrase and the Central DNA Flap in Human Immunodeficiency Virus Type 1 Nuclear Import J. Virol., October 25, 2002; 76(23): 12087 - 12096. [Abstract] [Full Text] [PDF] I. Hamaguchi, A. Ooka, A. Brun, J. Richter, N. Dahl, and S. Karlsson Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia Blood, September 26, 2002; 100(8): 2724 - 2731. [Abstract] [Full Text] [PDF] O. Ducrey-Rundquist, M. Guyader, and D. Trono Modalities of Interleukin-7-Induced Human Immunodeficiency Virus Permissiveness in Quiescent T Lymphocytes J. Virol., August 12, 2002; 76(18): 9103 - 9111. [Abstract] [Full Text] [PDF] T. VandenDriessche, L. Thorrez, L. Naldini, A. Follenzi, L. Moons, Z. Berneman, D. Collen, and M. K. L. Chuah Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo Blood, July 18, 2002; 100(3): 813 - 822. [Abstract] [Full Text] [PDF] N. Srinivasakumar, M. Zaboikin, T. Zaboikina, and F. Schuening Evaluation of Tat-Encoding Bicistronic Human Immunodeficiency Virus Type 1 Gene Transfer Vectors in Primary Canine Bone Marrow Mononuclear Cells J. Virol., June 14, 2002; 76(14): 7334 - 7342. [Abstract] [Full Text] [PDF] M. Maurice, E. Verhoeyen, P. Salmon, D. Trono, S. J. Russell, and F.-L. Cosset Efficient gene transfer into human primary blood lymphocytes by surface-engineered lentiviral vectors that display a T cell-activating polypeptide Blood, April 1, 2002; 99(7): 2342 - 2350. [Abstract] [Full Text] [PDF] A. Pfeifer, M. Ikawa, Y. Dayn, and I. M. Verma Transgenesis by lentiviral vectors: Lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos PNAS, February 19, 2002; 99(4): 2140 - 2145. [Abstract] [Full Text] [PDF] M. Scherr, K. Battmer, U. Blomer, B. Schiedlmeier, A. Ganser, M. Grez, and M. Eder Lentiviral gene transfer into peripheral blood-derived CD34+ NOD/SCID-repopulating cells Blood, January 15, 2002; 99(2): 709 - 712. [Abstract] [Full Text] [PDF]

	Copyright © 2000 by American Society of Hematology         Online ISSN: 1528-0020