《自然》：看华裔学者玩转DNA积木

　　

生物通报道：今天是六一儿童节，儿童最喜爱的玩具之一就是积木，这种流传已久的玩具不仅儿童喜爱，也有不少成人喜欢，近期一位华裔学者就玩起了DNA“积木”……

来自哈佛医学院，Wyss研究院等处的研究人员发表了题为“Complex shapes self-assembled from single-stranded DNA tiles”的文章，克服了之前的研究难题，提出了一种利用DNA“积木”设计的纳米设备，能将药物直接送至机体疾病所在之处。相关成果公布在Nature杂志上。

领导这一研究的是华裔科学家印鹏（Peng Yin，音译），这位科学家主要研究方向是基于触发分子几何学的工程生物成像探针，曾荣获2010年美国NIH院长创新奖。

众所周知，DNA是遗传信息的传递者，但是结构DNA纳米技术却利用了DNA作为遗传信息编码聚合物的优点，通过DNA分子卓越的自组装和识别能力实现精确的纳米构架，就如同纳米机械在工作一样。至今不少科学家们在这一领域获得了多项重要的研究成果。

目前大部分的研究主要集中在利用单个长链DNA构建形状，这种方法称之为DNA折纸，DNA折纸就像折叠一条长带子那样，把一条DNA长链反复折叠，形成需要的图形，就像用一根单线条绘制出整幅图画。折叠后的DNA长链，通过一些“钉子”对适当位置上的DNA短链加以固定，从而构建出了一张二维结构的精美图谱。

但是这种模块化的方法不适用于将大量小链组装成预先确定的、复杂的形状，在这篇文章中，研究人员研发了一种称为单链片（single-stranded tiles，SSTs，生物通译）的方法，这些单链结构能环环相扣，形成DNA“积木”，就像是乐高一样，通过编程，研究人员将这些单链片组装成精确的形状，比如字母或者表情，并且通过进一步发展，研究人员将这种技术用于研发新型纳米设备，能将药物直接送达疾病所在。

每个单链片包含有一个短的、独特的42-碱基DNA链，这个短链折叠成一个3nm*7nm的片状结构，附着到相邻的4个同样结构上，组成一个长方形结构。然后通过简单地将相对应的被目标形状覆盖的像素的那些链混合，再将没有相应像素的链排除，就可以生成一个形状。研究人员通过相对应的一个310像素组链，生成了超过100个各不相同的、复杂的二维形状，比如中国文字，数字等。

“利用DNA纳米技术构建可编程的纳米设备，是Wyss研究院的重点研究方向之一，因为我们确信这种方法在新型诊断和治疗方面的巨大潜力”，Wyss研究院第一任主任Donald Ingber说。

（生物通：张迪）

原文摘要：

Complex shapes self-assembled from single-stranded DNA tiles
Programmed self-assembly of strands of nucleic acid has proved highly effective for creating a wide range of structures with desired shapes1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25. A particularly successful implementation is DNA origami, in which a long scaffold strand is folded by hundreds of short auxiliary strands into a complex shape9, 14, 15, 16, 18, 19, 20, 21, 25. Modular strategies are in principle simpler and more versatile and have been used to assemble DNA2, 3, 4, 5, 8, 10, 11, 12, 13, 17, 23 or RNA7, 22 tiles into periodic3, 4, 7, 22 and algorithmic5 two-dimensional lattices, extended ribbons10, 12 and tubes4, 12, 13, three-dimensional crystals17, polyhedra11 and simple finite two-dimensional shapes7, 8. But creating finite yet complex shapes from a large number of uniquely addressable tiles remains challenging. Here we solve this problem with the simplest tile form, a ‘single-stranded tile’ (SST) that consists of a 42-base strand of DNA composed entirely of concatenated sticky ends and that binds to four local neighbours during self-assembly12. Although ribbons and tubes with controlled circumferences12 have been created using the SST approach, we extend it to assemble complex two-dimensional shapes and tubes from hundreds (in some cases more than one thousand) distinct tiles. Our main design feature is a self-assembled rectangle that serves as a molecular canvas, with each of its constituent SST strands—folded into a 3 nm-by-7 nm tile and attached to four neighbouring tiles—acting as a pixel. A desired shape, drawn on the canvas, is then produced by one-pot annealing of all those strands that correspond to pixels covered by the target shape; the remaining strands are excluded. We implement the strategy with a master strand collection that corresponds to a 310-pixel canvas, and then use appropriate strand subsets to construct 107 distinct and complex two-dimensional shapes, thereby establishing SST assembly as a simple, modular and robust framework for constructing nanostructures with prescribed shapes from short synthetic DNA strands.