title: HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene.
abstract: Highly active antiretroviral therapy (ART) has successfully turned Human immunodeficiency virus type 1 (HIV-1) from a deadly pathogen into a manageable chronic infection. ART is a lifelong therapy which is both expensive and toxic, and HIV can become resistant to it. An alternative to lifelong ART is gene therapy that targets the CCR5 co-receptor and creates a population of genetically modified host cells that are less susceptible to viral infection. With generic mathematical models we show that gene therapy that only targets the CCR5 co-receptor fails to suppress HIV-1 (which is in agreement with current data). We predict that the same gene therapy can be markedly improved if it is combined with a suicide gene that is only expressed upon HIV-1 infection.
authors.affiliation: Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, 3584CH, The Netherlands.
authors.forename: Aridaman
authors.initials: A
authors.lastname: Pandit
authors.affiliation: Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, 3584CH, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
mesh_terms: D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000235:genetics / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D018655:Lymphocyte Count; D008962:Models, Theoretical; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D019562:Viral Load
chemical_list: D019713:Receptors, CCR5