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Generation of CCR5-defective CD34 cells from ZFN-driven stop codon-integrated mesenchymal stem cell clones
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نویسنده
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manotham k. ,chattong s. ,setpakdee a.
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منبع
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journal of biomedical science - 2015 - دوره : 22 - شماره : 1
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چکیده
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Backgrounds: homozygous 32-bp deletion of the chemokine receptor 5 gene (ccr5) is associated with resistance to human immunodeficiency virus (hiv) infection,while heterozygosity delays hiv progression. bone marrow transplantation (bmt) from a 32/32 donor has been shown to cure an hiv-infected patient. however,the rarity of this mutation and the safety risks associated with current bmt protocols are the major obstacles to this treatment. zinc finger nuclease (zfn) targeting is a powerful method for achieving genomic disruption at specific dna sites of interest. results: taking advantage of the self-renewal and plasticity properties of stem cells,in this study,we successfully generated isogenic and six-cell clones of bone marrow-derived mesenchymal stem cells that carry the stop codon of the ccr5 gene by using a zfn-mediated homology-directed repair technique. these cells were expandable for more than 5 passages,and thus show potential to serve as an individual's cell factory. when oct4 was overexpressed,the mutated cells robustly converted to cd34+ progenitor cells. conclusion: we here reported the novel approach on generation of patients own cd34 cells from high fidelity zfn-mediated hdr msc clones. we believe that our approach will be beneficial in future hiv treatment. © 2015 manotham et al.; licensee biomed central.
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کلیدواژه
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CCR5; Genome editing; HIV; Mesenchymal stem cells; Zinc finger nuclease
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آدرس
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department of medicine,molecular and cell biology unit,lerdsin general hospital,bangkok, Thailand, department of medicine,molecular and cell biology unit,lerdsin general hospital,bangkok, Thailand, department of medicine,molecular and cell biology unit,lerdsin general hospital,bangkok, Thailand
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Authors
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