期刊
JOURNAL OF INFECTIOUS DISEASES
卷 208, 期 -, 页码 S160-S164出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit382
关键词
HIV; CCR5; hematopoietic stem cells; zinc finger nucleases; humanized mice
资金
- California Institute for Regenerative Medicine [DR1-01490]
- National Institutes of Health [HL073104]
- Swiss National Science Foundation
- California HIV/AIDS Research Program
- California Institute for Regenerative Medicine
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.
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