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Viruses 2015, 7(8), 4186-4203; doi:10.3390/v7082816

CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

1
Cellex GmbH, Fiedlerstr. 36, 01307 Dresden, Germany
2
Department of Cell Therapy, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic
3
Faculty of Medicine, University of New South Wales, Sydney 2052 NSW, Australia
4
Calimmune, Inc., Los Angeles, CA 90024, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 1 May 2015 / Revised: 3 July 2015 / Accepted: 22 July 2015 / Published: 27 July 2015
(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)
View Full-Text   |   Download PDF [407 KB, uploaded 27 July 2015]   |  

Abstract

Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape. View Full-Text
Keywords: HIV-1; CCR5; CCR5-delta32; tropism; gene therapy; viral escape; chemokine receptor HIV-1; CCR5; CCR5-delta32; tropism; gene therapy; viral escape; chemokine receptor
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hütter, G.; Bodor, J.; Ledger, S.; Boyd, M.; Millington, M.; Tsie, M.; Symonds, G. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape. Viruses 2015, 7, 4186-4203.

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