Abstract:
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.
journal_name
J Biomed Scijournal_title
Journal of biomedical scienceauthors
Manotham K,Chattong S,Setpakdee Adoi
10.1186/s12929-015-0130-6subject
Has Abstractpub_date
2015-03-26 00:00:00pages
25eissn
1021-7770issn
1423-0127pii
10.1186/s12929-015-0130-6journal_volume
22pub_type
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journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/1423-0127-16-92
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更新日期:2020-04-20 00:00:00
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journal_title:Journal of biomedical science
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