Zinc Finger Nuclease Editing of Hematopoietic Stem Cells as an Anti-HIV Therapy

Hematopoietic stem cell (HSC) transplanted humanized mice are a valuable small animal model for preclinical testing of HSC-based gene therapies, since the engraftment and subsequent differentiation of the cells in the mice allows a rigorous assessment of whether the genetic manipulation in any way impacts HSC function. In addition, since the HSC give rise to human CD4+ T cells, the mice can support an HIV-1 infection. This means that the mice are particularly suited to the evaluation of anti-HIV gene therapies, where the actual target human cell and gene therapy reagents can be evaluated in a system that supports infection by the authentic human virus. In this chapter we review the role played by humanized mouse models in the preclinical development of a promising anti-HIV approach based on disruption of the human CCR5 gene in human HSC, using zinc finger nuclease editing.