How to fold a DNA origami

17 August 2015

DNA origami is a technique that is used to create nanometre–scale shapes by folding strands of DNA. Writing in the journal Nature, a group of researchers from Condensed Matter Physics, Theoretical Physics and Computer Science at Oxford investigate how DNA origami folds.

DNA origami is made by annealing a set of short DNA staple strands with a long single-stranded template. Each staple is designed to bind to two or more specified domains of the template. The staples thus define a set of interaction rules that determine which parts of the template will be in close proximity in the folded structure. In a traditional DNA origami, each staple occupies a unique position in the structure giving a single well-folded state.

Relaxing the specificity of staple interactions so that each staple can bind in one of two configurations gives a system with a handful well-folded shapes and a vast number of misfolded states. It would be impossible to find well-folded configurations by a random search but, remarkably, this system gives a good yield of well-folded shapes. This result demonstrates the existence of efficient folding pathways – analogous to the folding landscape of proteins.
Changing the relative strength of long and short range interactions mediated by the staples can be used to guide the folding pathway toward specific folded shapes. These experiments validate a simple folding model which successfully predicts the dominant folding pathways observed in experiments.