Modifying nucleic acid nanostructures using triplex formation

利用三链体形成修饰核酸纳米结构

• 批准号: BB/H019219/1
• 负责人: Keith R Fox
• 金额: $ 44.09万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH019219%2F1
• 关键词: Modifying; nucleic; acid; nanostructures; using

In addition to its natural role in the storage of genetic information DNA is also an excellent material for constructing precise three-dimensional objects and assemblies on the nano-scale. By using the well-known base pairing of G with C and A with T, sequences of DNA can be easily designed so that they assemble into these structures forming precise shapes. In some cases it is possible to achieve nearly 100% yield by simply heating the sequences together in salty water and allowing the solution to cool back to room temperature. As a construction material DNA is also relatively easy and cheap to make, as well as being biodegradable and non-toxic. DNA has been used to construct containers capable of holding drugs and other biological molecules as well as devices capable of responding to different molecular signals. The next step is to develop a method of introducing different chemical or biological molecules within these DNA nano-structures. This would be useful, for example, in positioning different components within a DNA assembly to generate tiny 'nano' or 'bio' chips or to introduce a molecule onto a DNA cage capable of targeting it to a specific cell type, where it could then dispense its cargo. In this work we will develop such a method by exploiting the capacity of DNA to form three-stranded structures. These triplex structures are simply formed by adding a third strand of DNA to an existing double-stranded structure, where it attaches to the normal base pairs using specific triplet combinations. As the majority of DNA nano-structures are constructed from double-stranded segments it is possible to recognise these regions using a third strand of DNA, by generating a such three-stranded structure. Triplex formation is exquisitely specific and the third strand can therefore be designed to recognise a single region within a nanostructure. By attaching other molecules to this 'extra' strand it will be possible to position these at precise locations. The strategy can also be used to join nano-structures together, or to increase the rigidity of an existing structure. These complexes can also be easily disassembled by changing the conditions (i.e. increasing the pH). Our approach will offer a new general platform for producing many nanometer-scale structures and devices and will enable the design and synthesis of new supramolecular structures and materials.

除了它在存储遗传信息方面的天然作用外，DNA也是在纳米尺度上构建精确的三维物体和组件的极佳材料。通过使用众所周知的G与C和A与T的碱基配对，可以很容易地设计DNA序列，使它们组装成这些结构，形成精确的形状。在某些情况下，只需在盐水中将这些序列加热在一起，并允许溶液冷却到室温，就可以实现近100%的产率。作为一种建筑材料，DNA也相对容易和廉价，而且是可生物降解和无毒的。DNA已被用来构建能够容纳药物和其他生物分子的容器，以及能够响应不同分子信号的设备。下一步是开发一种方法，在这些DNA纳米结构中引入不同的化学或生物分子。例如，这将有助于在DNA组装中定位不同的组件，以产生微小的纳米或生物芯片，或者将分子引入能够针对特定细胞类型的DNA笼子，然后它可以在那里分配货物。在这项工作中，我们将开发这样一种方法，利用DNA形成三链结构的能力。这些三链结构是通过在现有的双链结构上添加第三条DNA而简单地形成的，在现有的双链结构中，它使用特定的三联组合连接到正常的碱基对上。由于大多数DNA纳米结构是由双链片段构建的，因此有可能通过产生这样的三链结构，使用第三条DNA识别这些区域。三链的形成是非常特殊的，因此第三链可以被设计成识别纳米结构中的单个区域。通过将其他分子连接到这条额外的链上，就有可能将这些分子定位在准确的位置。该策略还可以用于将纳米结构连接在一起，或者增加现有结构的刚性。通过改变条件(即提高pH值)，这些络合物也可以很容易地分解。我们的方法将为制造许多纳米级结构和器件提供一个新的通用平台，并将使新的超分子结构和材料的设计和合成成为可能。

项目成果

Functionalizing designer DNA crystals with a triple-helical veneer.

• DOI: 10.1002/anie.201309914
• 发表时间: 2014-04-07
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Rusling, David A.;Chandrasekaran, Arun Richard;Ohayon, Yoel P.;Brown, Tom;Fox, Keith R.;Sha, Ruojie;Mao, Chengde;Seeman, Nadrian C.
• 通讯作者: Seeman, Nadrian C.

Triplex-forming oligonucleotides: a third strand for DNA nanotechnology.

• DOI: 10.1093/nar/gkx1230
• 发表时间: 2018-02-16
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Chandrasekaran AR;Rusling DA
• 通讯作者: Rusling DA

DNA Conjugates and Sensors

DNA 缀合物和传感器

• 发表时间: 2012
• 作者: Kashida;H.; Asanuma;H.
• 通讯作者: H.

Sequence-specific recognition of DNA nanostructures.

DNA 纳米结构的序列特异性识别。

• DOI: 10.1016/j.ymeth.2014.02.028
• 发表时间: 2014
• 期刊: Methods (San Diego, Calif.)
• 作者: Rusling DA

Triplex-directed covalent cross-linking of a DNA nanostructure.

DNA 纳米结构的三重定向共价交联。

• DOI: 10.1039/c2cc35407a
• 发表时间: 2012
• 期刊: Chemical communications (Cambridge, England)
• 作者: Rusling DA