Nanoparticles for gene transfer to human embryonic stem cell colonies.

Nanoparticles for gene transfer to human embryonic stem cell colonies.
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DOI:
10.1021/nl8012665
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发表时间:
2008-10
期刊:
影响因子:
10.8
通讯作者:
Anderson DG
Anderson DG
中科院分区:
材料科学1区
文献类型:
--
作者:
Green JJ;Zhou BY;Mitalipova MM;Beard C;Langer R;Jaenisch R;Anderson DG

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我们开发可生物降解的聚合物纳米颗粒,以促进非病毒基因转移到人类胚胎干细胞(hESC)。小的(~ 200nm)和带正电的(~ 10mv)粒子是由阳离子的、可水解降解的聚氨基酯和质粒DNA自组装形成的。改变聚合物的端基可以调整所得纳米颗粒的生物物理特性及其基因传递效率。建立了OCT4驱动的GFP hES细胞系,可以快速识别纳米颗粒,促进基因转移,同时保持hESC未分化状态。利用这种细胞系统,我们合成的纳米颗粒的基因传递效率比市面上领先的转染剂Lipofectamine 2000高出四倍。重要的是,这些材料具有最小的毒性,不会对hES集落形态产生不利影响或导致非特异性分化。
We develop biodegradable polymeric nanoparticles to facilitate non-viral gene transfer to human embryonic stem cells (hESC). Small (~200 nm) and positively charged (~10 mV) particles are formed by the self-assembly of cationic, hydrolytically-degradable, poly(beta-amino esters) and plasmid DNA. Varying the end-group of the polymer can tune the biophysical properties of the resulting nanoparticles and their gene delivery efficacy. An OCT4 driven GFP hES cell line was created to allow rapid identification of nanoparticles that facilitate gene transfer while maintaining an hESC undifferentiated state. Using this cell system, we synthesized nanoparticles that have gene delivery efficacy up to four times higher than the leading commercially available transfection agent, Lipofectamine 2000. Importantly, these materials have minimal toxicity and do not adversely affect hES colony morphology or cause non-specific differentiation.
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