丁宝全最新《科学》文章：首次获得DNA芯片纳米设备

　　

生物通报道：来自纽约大学化学系Ned Seeman实验室的研究人员通过一个纳米机械设备插入整合进DNA芯片获得了一个“DNA盒”（DNA cassette），这个“盒子”可以用于驱动一个纳米机器人（nanorobotics）的臂膀，这是首次科学家们能够在一个DNA芯片上用到有功能的纳米科技设备。这一研究成果公布在12月8日《Science》杂志上。

完成这一研究的是纽约大学的Nadrian C. Seeman教授和他的研究生丁宝全（Baoquan Ding）。

原文摘要：
Science 8 December 2006:
Vol. 314. no. 5805, pp. 1583 - 1585
DOI: 10.1126/science.1131372
Operation of a DNA Robot Arm Inserted into a 2D DNA Crystalline Substrate  [Abstract]

纳米生物学的近期设想是在纳米尺度上应用生物学原理，发现新现象，研制可编程的分子机器人，也称纳米机器人。纳米机器人的研制属于分子仿生学的范畴，它是根据分子水平的生物学原理为设计原型，设计制造可对纳米空间进行操作的“功能分子器件”。纳米机器人是纳米生物学中最具有诱惑力的内容，这种机械可以注入人体血管内，进行健康检查和疾病治疗。还可以用来进行人体器官的修复工作、作整容手术、从基因中除去有害的DNA，或把正常的DNA安装在基因中，使机体正常运行等等。

这种纳米机器人需要精确的定位和特殊纳米设备的操作，由于DNA具有结构上的可编程性，因此成为了纳米机器人的一种独具吸引力的系统。在这篇文章中，研究人员获得了一个能将序列依赖性（sequence-dependent）有力的DNA机械手（robot arm）插入一个二维的水晶DNA芯片（crystalline DNA array）中的“DNA盒子”，通过原子力显微镜(Atomic Force Microscopy，AFM）研究人员证明了这种装置在整合后是完全有效的。

这种装置是基于之前由纽约大学的一名为廖士平（Shiping Liao，音译）的研究生主导发明的一种能使DNA序列进行翻译的设备，因此潜在的成为了一种组装新材料构建“砖石”的“加工工厂”。这种发明能用于制造新合成纤维，发展信息加密技术（encryption of information），也可以用于DNA计算（DNA-based computation）。

然而虽然这种设备能模仿DNA序列拷贝出来的RNA序列，从而被翻译成蛋白序列的过程，但是控制纳米机械工具信号的是DNA而不是RNA，因此在这一篇研究报告中，Ding等人在之前的基础上构建了一个包含绑定位点——“DNA盒”——的构架，这就能让这种设备插入到一个DNA芯片的特异性位点，改变“DNA盒”的调控序列或插入序列，研究人员就能操作芯片，或者将其插入到不同的位置。同时研究人员也在构架中加了一个长手臂，使得他们可以观察到half-rotation之后的结构——这主要是通过原子力显微镜完成的。
（生物通：张迪）

附：
Ned Seeman's Laboratory 


Our laboratory is investigating unusual DNA molecules in model systems that use synthetic molecules. A major effort in our laboratory is devoted to DNA Nanotechnology.The attachment of specific sticky ends to a DNA branched junction enables the construction of stick figures, whose edges are double-stranded DNA. This approach has already been used to assemble a cube, a truncated octahedron , nanomechanical devices and 2-D crystals from DNA. Ultimate goals for this approach include the assembly of a biochip computer, nanorobotics and the rational synthesis of periodic matter. This methodology also has applications to DNA Based Computing. 

Our interest in branched DNA was originally stimulated by a desire to characterize Holliday junctions. These are four-arm branched DNA molecules that are found to be structural intermediates in genetic recombination. The focus of the work on these unusual molecules is to characterize the biophysics of recombination intermediates, particularly their structure, dynamics and thermodynamics, and to establish the relationship between these properties and their biological function. In the last few years, the symmetry, crossover topology and sequence-dependent thermodynamics of the 4-arm junction have been characterized and analyzed. The study of recombination intermediates has been extended by constructing and analyzing molecules with double crossovers, and by exploring broader classes of multi-stranded molecules, called antijunctions and mesojunctions. Recently, we have used Bowtie junctions to examine the properties of Holliday junctions.

Knotted DNA molecules have also been constructed, because they are recombination intermediate analogs, because they offer a window on stressed DNA, and because they may permit us to clone the complex catenanes that we make in our DNA nanotechnology program. The program on single-stranded Nucleic Acid Topology has led to characterization of the interactions of synthetic DNA knots with topoisomerases, to a general algorithm for the construction of any DNA knot, to the synthesis of a DNA molecule that can be built to yield four different topological species , to the discovery of an RNA topoisomerase, and to the construction of Borromean Rings.

The physical techniques used in the laboratory include X-ray crystallography, computer graphics-aided molecular modeling and design, AFM, FRET, gel electrophoresis and automated oligonucleotide synthesis. Our published work in these areas is summarized in the Structural Studies Bibliography.