Programmed self-assembly of strands of nucleic acid has proved highly effective for creating a wide range of structures with desired shapes. A particularly successful implementation is DNA origami, in which a long scaffold strand is folded by hundreds of short auxiliary strands into a complex shape. Modular strategies are in principle simpler and more versatile and have been used to assemble DNA or RNA tiles into periodic and algorithmic two-dimensional lattices, extended ribbons and tubes three-dimensional crystals, polyhedra11 and simple finite two-dimensional shapes. 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-assembly. Although ribbons and tubes with controlled circumferences 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.
DNA shapes (Image: Bryan Wei, Mingjie Dai and Peng Yin, Wyss Institute for Biologically Inspired Engineering at Harvard University)
New Scientist – Long DNA strands had typically come from a virus, which raises the possibility that the body will attack the structures. Now, Peng Yin and colleagues at Harvard University have designed a similar technology that relies entirely on synthetic DNA. “Our structures could be made to be highly biocompatible,” he says.
Instead of folding one long strand of viral DNA, Yin’s team designed short synthetic DNA strands that can fold into a small tile, just 7 by 3 nanometres in size. “Each tile acts like a Lego block,” he says. Tiles automatically interlock with neighbouring tiles that carry a complementary DNA sequence. This means that with a bit of forward planning, the team could design a complete set of tiles that lock together to create more than 100 shapes – including any letter of the alphabet.
The synthetic DNA shapes could dodge the immune system, buying them more time to shuttle drugs to the right tissue
Self-assembly of SST rectangles and tubes
Simple shapes designed using a molecular canvas.