Science 355, eaam5488 (2017)

DNA origami can potentially be used to control the spatial arrangement of molecules in living systems, but cells are challenging environments for DNA origami, due to the lack of single-stranded DNA and the need for a high annealing temperature. Praetorius and Dietz now report a way of folding double-stranded DNA templates into defined nanostructures in vitro, a first step towards in vivo conditions. Instead of using oligonucleotide staples, common in DNA origami, two parallel DNA double strands are stitched together by staple proteins originated from transcription activator-like (TAL) effector proteins.

Praetorius and Dietz synthesize twelve different staple proteins by programming the genes that encode TAL effectors — each staple protein can recognize a specific DNA sequence. By designing the sequences of the template DNA using a polymerase chain reaction, the scientists fabricate various desired hybrid structures at room temperature. Moreover, the synthesis can be carried out in one pot containing the genes encoding the staple proteins, RNA polymerase, ribosomes, cofactors for transcription and translation, and the double-stranded DNA scaffold. The encoded staple proteins self-assemble with the parallel DNA double strand, forming the desired DNA–protein–hybrid nanostructure. With this method, proteins with different functionalities can also be easily integrated into hybrid nanostructures and their spatial arrangement can be accurately controlled.