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Stem-Cell-Based Gene Therapy for HIV Infection
Viruses 2014, 6(1), 54-68; doi:10.3390/v6010054

CCR5 as a Natural and Modulated Target for Inhibition of HIV

1,*  and 2,3
1 Calimmune, Inc., Los Angeles, California, CA 90024, USA 2 Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, 68167 Mannheim, Germany 3 Cellex GmbH, 01307 Dresden, Germany
* Author to whom correspondence should be addressed.
Received: 2 September 2013 / Revised: 2 December 2013 / Accepted: 11 December 2013 / Published: 30 December 2013
(This article belongs to the Special Issue Gene Therapy for Retroviral Infections)
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Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection—this without detrimental effects to the host—and transplantation of CCR5-delta32 stem cells in a patient with HIV (“Berlin patient”) achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells.
Keywords: CCR5; C46; gene therapy; HIV; stem cell transplantation CCR5; C46; gene therapy; HIV; stem cell transplantation
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Burke, B.P.; Boyd, M.P.; Impey, H.; Breton, L.R.; Bartlett, J.S.; Symonds, G.P.; Hütter, G. CCR5 as a Natural and Modulated Target for Inhibition of HIV. Viruses 2014, 6, 54-68.

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