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   Generation of CCR5-defective CD34 cells from ZFN-driven stop codon-integrated mesenchymal stem cell clones  
   
نویسنده manotham k. ,chattong s. ,setpakdee a.
منبع journal of biomedical science - 2015 - دوره : 22 - شماره : 1
چکیده    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.
کلیدواژه CCR5; Genome editing; HIV; Mesenchymal stem cells; Zinc finger nuclease
آدرس 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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