Non-covalent Single Transcription Factor Encapsulation Inside a DNA Cage
Non-covalent Single Transcription Factor Encapsulation Inside a DNA Cage
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DNA 笼内非共价单转录因子封装
DOI：
10.1002/ange.201207914
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发表时间：
2013
影响因子：
--
通讯作者：
Crawford R
中科院分区：
文献类型：
--
作者：
Crawford R
基因表达的调节是细胞发育、维持和生长的基础。基因调控主要发生在转录水平，主要由称为转录因子（TF）的DNA结合蛋白控制。例如，仅向完全分化的细胞递送四个TF就可以使它们恢复到干细胞样状态，为再生医学提供了希望。[1]通过调节细胞内TF水平来影响基因调控的能力将构成用于研究调控途径或开发治疗应用的有力方法。[2]An控制基因表达的一个极好的方法是将TF可逆地包封在药物递送笼中。在笼子里，TF不能结合细胞DNA并且是无活性的;然后可以使用外部触发器打开笼子，释放并因此激活TF。用于封装的分子笼在尺寸和制造方法上各不相同：富勒烯（约1 nm）可以封装单个原子;[3]中空金属纳米颗粒[4]（约100 nm）用于蛋白质;脂质体（100-800 nm）用于药物[5]或荧光分子。[6]最近有报道称，TF被超分子纳米颗粒（约50 nm）包裹用于细胞内递送。[7]在此，我们报告了一种新的笼TF使用DNA构建。DNA笼具有许多优点：例如，可以合理地设计尺寸类似于蛋白质靶标的笼，以便在单个，快速和容易的步骤中进行自组装。这种DNA纳米结构的例子从多面体[8]到基于DNA折纸的更大的结构。[9]第一章
Regulation of gene expression is fundamental for cell development, maintenance, and growth. Gene regulation occurs mainly at the level of transcription, controlled primarily by DNA-binding proteins known as transcription factors (TFs). For example, the delivery of just four TFs to fully differentiated cells can cause them to revert to a stemcell-like state, offering promise for regenerative medicine.[1] The ability to influence gene regulation by tuning intracellular TF levels would constitute a powerful method for the study of regulation pathways or the development of therapeutic applications.[2]An elegant approach to the control of gene expression is to reversibly encapsulate the TFs in a drug-delivery cage. Within the cage, the TF cannot bind cellular DNA and is inactive; the cage can then be opened using external triggers, releasing and thus activating the TF. Molecular cages designed for encapsulation vary in size and fabrication method: fullerenes (approximately 1nm) can encapsulate single atoms;[3] hollow metal nanoparticles [4](approximately 100 nm) for proteins; and liposomes (100–800 nm) for drugs [5] or fluorescent molecules.[6] TF encapsulation by supramolecular nanoparticles (approximately 50nm) for intracellular delivery has recently been reported.[7] Herein, we report a novel cage for a TF constructed using DNA. A DNA cage offers many advantages: for example, cages of dimensions similar to protein targets can be designed rationally to self-assemble in a single, rapid, and facile step. Examples of such DNA nanostructures range from polyhedra,[8] to much larger structures based on DNA origami.[9]