AI Article Synopsis

  • Research is focused on developing genetic strategies to block the CCR5 co-receptor, which is essential for HIV-1 infection, as a therapy for HIV.
  • Hematopoietic stem/precursor cells (HSPC) can be modified to lack CCR5 using zinc finger nucleases (ZFNs), allowing for the creation of HIV-resistant CD4(+) T cells after transplantation.
  • The effectiveness and safety of these gene therapies can be tested by transplanting ZFN-treated HSPC into immunodeficient mice, which serve as a useful model for studying their potential against HIV.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807977PMC
http://dx.doi.org/10.1093/infdis/jit382DOI Listing

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