Targeted Elimination of Tumorigenic Human Pluripotent Stem Cells Using Suicide-Inducing Virus-like Particles.
Targeted Elimination of Tumorigenic Human Pluripotent Stem Cells Using Suicide-Inducing Virus-like Particles.
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DOI：
10.1021/acschembio.8b00490
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发表时间：
2018-08-17
影响因子：
4
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Rampoldi A;Crooke SN;Preininger MK;Jha R;Maxwell J;Ding L;Spearman P;Finn MG;Xu C
通过自杀基因的转基因表达对前药致敏是再生医学中选择性消除潜在致瘤性人多能干细胞（hPSC）的主要策略，但转基因修饰带来安全风险，例如有害的诱变。我们在此描述了一种使用病毒样颗粒（VLP）将自杀诱导分子明确递送至hPSC的替代方法，并证明了其在体外消除未分化hPSC中的用途。从Qβ噬菌体衣壳改造VLP以含有增强的绿色荧光蛋白（EGFP）或胞嘧啶脱氨酶（CD），并同时展示多个IgG结合ZZ结构域。在用针对hPSC特异性表面聚糖SSEA-5的抗体标记后，显示含EGFP的颗粒特异性结合培养物中的未分化细胞，并且含CD的颗粒能够消除未分化的hPSC，在用前药5-氟胞嘧啶处理后对分化细胞几乎没有细胞毒性。
Sensitization to prodrugs via transgenic expression of suicide genes is a leading strategy for the selective elimination of potentially tumorigenic human pluripotent stem cells (hPSCs) in regenerative medicine, but transgenic modification poses safety risks such as deleterious mutagenesis. We describe here an alternative method of delivering suicide-inducing molecules explicitly to hPSCs using virus-like particles (VLPs), and demonstrate its use in eliminating undifferentiated hPSCs in vitro. VLPs were engineered from Qβ bacteriophage capsids to contain enhanced green fluorescent protein (EGFP) or cytosine deaminase (CD), and to simultaneously display multiple IgG-binding ZZ domains. After labeling with antibodies against the hPSC-specific surface glycan SSEA-5, EGFP-containing particles were shown to specifically bind undifferentiated cells in culture, and CD-containing particles were able to eliminate undifferentiated hPSCs with virtually no cytotoxicity to differentiated cells upon treatment with the prodrug 5-fluorocytosine.
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影响因子：
6.2
作者：
Rhee JK;Hovlid M;Fiedler JD;Brown SD;Manzenrieder F;Kitagishi H;Nycholat C;Paulson JC;Finn MG
通讯作者：
Finn MG
影响因子：
56.9
作者：
Korkegian, A;Black, ME;Stoddard, BL
通讯作者：
Stoddard, BL
影响因子：
7.5
作者：
Malecki M
通讯作者：
Malecki M
影响因子：
48
作者：
Burridge, Paul W.;Matsa, Elena;Shukla, Praveen;Lin, Ziliang C.;Churko, Jared M.;Ebert, Antje D.;Lan, Feng;Diecke, Sebastian;Huber, Bruno;Mordwinkin, Nicholas M.;Plews, Jordan R.;Abilez, Oscar J.;Cui, Bianxiao;Gold, Joseph D.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
DOI：
10.1073/pnas.93.12.5688
发表时间：
1996-06-11
影响因子：
11.1
作者：
Braisted, AC;Wells, JA
通讯作者：
Wells, JA