Heterochiral DNA Strand-Displacement Circuits

• Published in: Journal of the American Chemical Society 2017-12, Vol.139 (49), p.17715-17718
• Main Authors: Kabza, Adam M, Young, Brian E, Sczepanski, Jonathan T
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.7b10038

The absence of a straightforward strategy to interface native d-DNA with its enantiomer l-DNAoligonucleotides of opposite chirality are incapable of forming contiguous Watson–Crick base pairs with each otherhas enforced a “homochiral” paradigm over the field of dynamic DNA nanotechnology. As a result, chirality, a key intrinsic property of nucleic acids, is often overlooked as a design element for engineering of DNA-based devices, potentially limiting the types of behaviors that can be achieved using these systems. Here we introduce a toehold-mediated strand-displacement methodology for transferring information between orthogonal DNA enantiomers via an achiral intermediary, opening the door for “heterochiral” DNA nanotechnology having fully interfaced d-DNA and l-DNA components. Using this approach, we demonstrate several heterochiral DNA circuits having novel capabilities, including autonomous chiral inversion of DNA sequence information and chirality-based computing. In addition, we show that heterochiral circuits can directly interface endogenous RNAs (e.g., microRNAs) with bioorthogonal l-DNA, suggesting applications in bioengineering and nanomedicine. Overall, this work establishes chirality as a design parameter for engineering of dynamic DNA nanotechnology, thereby expanding the types of architectures and behaviors that can be realized using DNA.