Intracellular trafficking of polyamidoamine-poly(ethylene glycol) block copolymers in DNA delivery.
Intracellular trafficking of polyamidoamine-poly(ethylene glycol) block copolymers in DNA delivery.
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DOI：
10.1021/bc200059v
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发表时间：
2011-08-17
影响因子：
4.7
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Bonner, Daniel K.;Leung, Cheuk;Chen-Liang, Jane;Chingozha, Loice;Langer, Robert;Hammond, Paula T.
核酸的传递有可能通过允许临床解决以前无法治疗的疾病来彻底改变医学。病毒递送系统已经显示出免疫原性和毒性危险，但是合成载体在转染效率方面滞后。以前，我们已经开发了一种模块化的，线性树枝状嵌段共聚物结构，与商业标准相比具有高基因转染效率。这种合理设计的系统利用阳离子树枝状块来缩合阴离子DNA，并形成具有有利的内体逃逸性质的复合物。线性嵌段提供生物相容性，保护免受血清蛋白的影响，并且可以用靶向配体官能化。在这项工作中，我们定量的性能，该系统相对于细胞内的障碍，基因传递使用高通量和传统的方法。描述了一种基于图像的高通量内体逃逸测定法，并将其应用于嵌段共聚物系统。经证明，核进入是更有效运载的最大障碍，将在该系统的未来版本中加以解决。
The delivery of nucleic acids has the potential to revolutionize medicine by allowing previously untreatable diseases to be clinically addressed. Viral delivery systems have shown immunogenicity and toxicity dangers, but synthetic vectors have lagged in transfection efficiency. Previously, we have developed a modular, linear-dendritic block copolymer architecture with high gene transfection efficiency compared to commercial standards. This rationally designed system makes use of a cationic dendritic block to condense the anionic DNA and forms complexes with favorable endosomal escape properties. The linear block provides biocompatibility, protection from serum proteins, and can be functionalized with a targeting ligand. In this work, we quantitate performance of this system with respect to intracellular barriers to gene delivery using both high-throughput and traditional approaches. An image-based, high throughput assay for endosomal escape is described and applied to the block copolymer system. Nuclear entry is demonstrated to be the most significant barrier to more efficient delivery and will be addressed in future versions of the system.
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影响因子：
5.1
作者：
Dash, PR;Read, ML;Seymour, LW
通讯作者：
Seymour, LW
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14.9
作者：
Hama S;Akita H;Iida S;Mizuguchi H;Harashima H
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Harashima H
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Gabrielson, Nathan P.;Pack, Daniel W.
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Pack, Daniel W.
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Jones, RA;Cheung, CY;Wilson, MR
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Wilson, MR
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作者：
Akita, H;Ito, R;Harashima, H
通讯作者：
Harashima, H