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HDAC inhibitors improve CRISPR-mediated HDR editing efficiency in iPSCs

Science China(Life Sciences) 2021年第9期64卷 1449-1462页

作者： Jian-Ping Zhang Zhi-Xue Yang Feng Zhang Ya-Wen Fu Xin-Yue Dai Wei Wen Beldon Zhang Hannah Choi Wanqiu Chen Meredith Brown david baylink Lei Zhang Hongyu Qiu Charles Wang Tao Cheng Xiao-Bing Zhang State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China School of Medicine Loma Linda UniversityLoma LindaCA 92354USA Center for Genomics School of MedicineLoma Linda UniversityLoma LindaCA 92350USA CAMS Key Laboratory of Gene Therapy for Blood Diseases Tianjin 300020China Center for Stem Cell Medicine Chinese Academy of Medical SciencesTianjin 300020China Department of Stem Cell&Regenerative Medicine Peking Union Medical CollegeTianjin 300020China Tianjin Key Laboratory of Gene Therapy for Blood Diseases Tianjin 300020China Center of Molecular and Translational Medicine Institution of Biomedical ScienceGeorgia State UniversityAtlantaGA 30303USA

Genome-edited human induced pluripotent stem cells(iPSCs)hold great promise for therapeutic ***,low editing efficiency has hampered the applications of CRISPR-Cas9 technology in creating knockout and homology-directed repair(HDR)-edited iPSC lines,particularly for silent *** is partially due to chromatin compaction,inevitably limiting Cas9 access to the target *** the six HDAC inhibitors we examined,vorinostat,or suberoylanilide hydroxamic acid(SAHA),led to the highest HDR efficiency at both open and closed loci,with acceptable *** inhibitors equally increased non-homologous end joining(NHEJ)editing efficiencies(~50%)at both open and closed loci,due to the considerable HDAC inhibitor-mediated increase in Cas9 and sgRNA ***,we observed more substantial HDR efficiency improvement at closed loci relative to open chromatin(2.8 vs.1.7-fold change).These studies provide a new strategy for HDRediting of silent genes in iPSCs.

关键词： HDAC inhibitors CRISPR-Cas9 genome editing iPSC

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Effect of aging on stem cells

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World Journal of Experimental Medicine 2017年第1期7卷 1-10页

作者： Abu Shufian Ishtiaq Ahmed Matilda HC Sheng Samiksha Wasnik david J baylink Kin-Hing William Lau Regenerative Medicine Unit Department of MedicineLoma Linda University School of Medicine Musculoskeletal Disease Center Jerry L.Pettis Memorial VA Medical Center

Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of agingassociated disorders, but also in future development of novel effective stem cell-based therapies to treat agingassociated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects.

关键词： Aging Biological aging Cellular aging Adult stem cells Premature aging Mesenchymal stem cell Stem cell renewal Tissue regeneration

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Synthesis of Magnetic Nanoparticles for Application of Retroviral Vectors Mediated Gene Therapy

Synthesis of Magnetic Nanoparticles for Application of Retro...

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中国颗粒学会2004年年会暨海峡两岸颗粒技术研讨会会议

作者： K.-H.William Lau david baylink Shin-Tai Chen Masculoskeletal Diseases Center J.L.Pettis VA Medical CenterLoma LindaCA92357USA) Masculoskeletal Diseases Center J.L.Pettis VA Medical CenterLoma LindaCA92357USA) Masculoskeletal Diseases Center J.L.Pettis VA Medical CenterLoma LindaCA92357USA)

＜正＞Successful gene therapy depends on accurate delivery of therapeutic genes to target sites. In this report, we used magnetic nanoparticles to achieve this goal by developing magnetic Moloney leukemia virus-based （MRV） vectors. The vectors are combined by magnetic nanoparticles with the MRV viral vectors and can be guided to a specific site by an external magnetic filed.

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Synthesis of Magnetic Nanoparticles for Application of Retroviral Vectors Mediated Gene Therapy

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过程工程学报 2004年第Z1期4卷 122-122页

作者： Huan-Chiu Ku Ming-Fong Tai K.-H. William Lau david baylink Shin-Tai Chen Department of Physics Ting-Hua University Hsin-Chu China Department of Physics WeFeng Institute of Technology Chia-yi China Musculoskeletal Diseases Center J. L. Pettis VA Medical Center Loma Linda CA 92357 USA

　　Successful gene therapy depends on accurate delivery of therapeutic genes to target sites. In this report, we used magnetic nanopartieles to achieve this goal by developing magnetic Moloney leukemia virus-based (MRV) vectors. The vectors are combined by magnetic nanoparticles with the MRV viral vectors and can be guided to a specific site by an external magnetic filed.……

关键词： Gene Therapy Retroviral Vectors magnetic nanoparticles gene therapy

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