Algorithmic design of cotranscriptionally folding 2D RNA origami structures

We address a biochemical folding obstacle of “polymerase trapping” that arises in the remarkable RNA origami tile design framework of Geary, Rothemund and Andersen (Science 2014). We present a combinatorial formulation of this obstacle, together with an optimisation procedure that yields designs minimising the risk of encountering the corresponding topological trap in the tile folding phase. The procedure has been embedded in an automated software pipeline, and we provide examples of designs produced by the software, including an optimised version of the RNA smiley-face tile proposed by Geary and Andersen (DNA 2014).Peer reviewe