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Viruses 2014, 6(1), 243-263; doi:10.3390/v6010243

Gene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1

1 Centre for Gene Therapy, Institute of Child Health, University College London, London WC1N 1EH, UK 2 MRC Centre for Medical Molecular Virology, University College London, London WC1E 6BT, UK
* Author to whom correspondence should be addressed.
Received: 24 October 2013 / Revised: 20 December 2013 / Accepted: 6 January 2014 / Published: 14 January 2014
(This article belongs to the Special Issue Gene Therapy for Retroviral Infections)
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Restriction factors are a collection of antiviral proteins that form an important aspect of the innate immune system. Their constitutive expression allows immediate response to viral infection, ahead of other innate or adaptive immune responses. We review the molecular mechanism of restriction for four categories of restriction factors; TRIM5, tetherin, APOBEC3G and SAMHD1 and go on to consider how the TRIM5 and TRIMCyp proteins in particular, show promise for exploitation using gene therapy strategies. Such approaches could form an important alternative to current anti-HIV-1 drug regimens, especially if combined with strategies to eradicate HIV reservoirs. Autologous CD4+ T cells or their haematopoietic stem cell precursors engineered to express TRIMCyp restriction factors, and provided in a single therapeutic intervention could then be used to restore functional immunity with a pool of cells protected against HIV. We consider the challenges ahead and consider how early clinical phase testing may best be achieved.
Keywords: HIV; gene therapy; restriction factor; TRIM; cyclophilin; TRIMCyp HIV; gene therapy; restriction factor; TRIM; cyclophilin; TRIMCyp
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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Chan, E.; Towers, G.J.; Qasim, W. Gene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1. Viruses 2014, 6, 243-263.

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