Molecular Logic Gates on DNA Origami Nanostructures for MicroRNA Diagnostics

Abstract

Molecular computing holds great promise for diagnosis and treatment of diseases at the molecular level; nevertheless, designing molecular logic gates to operate programmably and autonomously for molecular diagnostics still remains challenging. We designed logic gates on DNA Origami for microRNA analysis. As a demonstration, two indicators of heart failure, microRNA-21 and microRNA-195, were selected as the logic inputs. The logic gates contain two main modules: computation module and output module, performing in a single DNA Origami nanostructure. The computation module recognizes disease indicators, while the output module display different nanoscale symbols, "+" (positive) or "-" (negative), depending on the computing results. We demonstrated that the molecular logic gates worked well with single and two input combinations.

Engineering Cell Surface Function with DNA Origami

“…In the future, these membrane bound DNA origami structures could enable programmed assembly within the membrane to mimic functional biomolecular complexes such as an immune synapse, especially given the wide use of DNA origami to template or organize proteins [34] . Moreover, given the rapidly growing scope of DNA nanotechnology, our MBB will enable the capability to implement numerous DNA device functions such as measurement of molecular forces [17] , programmed motion and conformational changes [30] , sensing of extracellular target molecules [13] , intracellular pH measurements [35] , and local delivery of molecular payloads [10] at the surface of cells in their complex local environments. The characteristics of the MBB presented here, including the size and overhang binding specificity, could also allow for localization of many measurement functionalities on the same or distinct platforms on individual cells or imparting specific functions to certain cell types within mixed cell populations in lab-on-a-chip environments.…”

“…DNA origami devices have wide-ranging applications including drug delivery [10–12] , sensing [13, 14] , molecular manipulation [15] , and measurement [16, 17] .…”

DNA Origami: Folded DNA‐Nanodevices That Can Direct and Interpret Cell Behavior

“…One sophisticated example of a DNA origami logic gate for diagnostic purposes is based on the idea of staple tethering and strand displacement ( Figure 6 ) [65] . When the correct miRNA signals are detected in solution, they bind staple tethers and release a biotin tagged output strand.…”

Lineal DNA logic gate for microRNA diagnostics with strand displacement and fluorescence resonance energy transfer

“…DNA logic gates, the basis of logic operations and the core components in molecular computers, hold great promise for gene regulation, biomarker detection and molecular diagnostics that have become more and more important to human cancers, genetic disease, and infectious diseases [1][2][3][4][5][6]. Various DNA logic gates have been developed [7][8][9][10][11][12].…”

“…Wang et al designed a series of DNA logic gates based on toehold-mediated strand displacement and Gquadruplex that can autonomously control the coalescence and release of PPIX in vitro, an important molecule in photodynamic diagnosis and therapy [8]. Song et al constructed logic gates based on two DNA origami nanostructures to perform microRNA analysis [3]. Willner et al designed a series of logic gates using DNA scaffold, which are activated by either adenosine monophosphate or cocaine [9].…”