1. Gene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1
- Author
-
Waseem Qasim, Greg J. Towers, and Emma Chan
- Subjects
CD4-Positive T-Lymphocytes ,Ubiquitin-Protein Ligases ,Genetic enhancement ,lcsh:QR1-502 ,HIV Infections ,Review ,restriction factor ,Biology ,Bioinformatics ,lcsh:Microbiology ,Antiviral Restriction Factors ,Tripartite Motif Proteins ,TRIM ,Immune system ,Immunity ,Virology ,Humans ,APOBEC3G ,Innate immune system ,HIV ,Genetic Therapy ,gene therapy ,3. Good health ,Infectious Diseases ,cyclophilin ,HIV-1 ,Tetherin ,Stem cell ,Carrier Proteins ,TRIMCyp ,SAMHD1 - Abstract
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. more...
- Published
- 2014
- Full Text
- View/download PDF