title: Pre-clinical modeling of CCR5 knockout in human hematopoietic stem cells by zinc finger nucleases using humanized mice.
abstract: Genetic strategies to block expression of CCR5, the major co-receptor of human immunodeficiency virus type 1 (HIV-1), are being developed as anti-HIV therapies. For example, human hematopoietic stem/precursor cells (HSPC) can be modified by the transient expression of CCR5-targeted zinc finger nucleases (ZFNs) to generate CCR5-negative cells, which could then give rise to HIV-resistant mature CD4(+) T cells following transplantation into patients. The safety and anti-HIV effects of such treatments can be evaluated by transplanting ZFN-treated HSPC into immunodeficient mice, where the extent of human cell engraftment, lineage differentiation and anti-HIV activity arising from the engineered HSPC can be examined. In this way, humanized mice are providing a powerful small animal model for pre-clinical studies of novel anti-HIV therapies.
authors.affiliation: Keck School of Medicine of the University of Southern California, Los Angeles.
authors.forename: Ursula
authors.initials: U
authors.lastname: Hofer
authors.forename: Jill E
authors.initials: JE
authors.lastname: Henley
authors.forename: Colin M
authors.initials: CM
authors.lastname: Exline
authors.forename: Orla
authors.initials: O
authors.lastname: Mulhern
authors.forename: Evan
authors.initials: E
authors.lastname: Lopez
authors.forename: Paula M
authors.initials: PM
authors.lastname: Cannon
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000009:adverse effects / Q000379:methods*; D015658:HIV Infections / Q000628:therapy* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000821:virology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics*; D015728:Receptors, HIV / Q000172:deficiency / Q000235:genetics*; D016335:Zinc Fingers
chemical_list: D019713:Receptors, CCR5; D015728:Receptors, HIV
keywords: CCR5; HIV; hematopoietic stem cells; humanized mice; zinc finger nucleases