Rational Design of Framework Nucleic Acids for Bioanalytical Applications

Abstract

With the advent of DNA nanotechnology, nucleic acids have been used building blocks for constructing various DNA nanostructures. As classical and simple DNA nanostructures, framework nucleic acids (FNAs) have attracted enormous attention in the field of biosensing. The sequence‐specific self‐assembly properties and high programmability of nucleic acids allow FNAs to be incorporated in advanced probe design. In addition, FNAs enable the engineering of surfaces for biosensing (e. g., probe orientation, probe spacing), thereby improving the accessibility of target molecules to the probes arranged on heterogeneous surfaces. Moreover, FNAs offer a universal and promising platform for sensing cellular molecules because of their prominent biocompatibility and cellular permeability. Herein recent advances in FNA‐based biosensors are summarized, including electrochemical detection, optical detection, and intracellular sensing. It is hoped that this review will provide guidelines for the design and construction of FNA scaffold‐based biosensors.

Rationally Engineered Nucleic Acid Architectures for Biosensing Applications

“…The exploitation of DNA as a material building block to create DNA nanostructures with controlled geometries and spatial configurations has elicited tremendous interest since Seeman’s proposal in the early 1980s. ,, The precise self-recognition capability of nucleic acids contributes to assembly of a variety of DNA motifs and complexes ranging from a few nanometers to micrometers. , Moreover, engineering complex DNA nanostructures with twists and curves can be achieved by targeted insertions and deletions of bases to control their flexibility and stress . More importantly, the DNA origami technology provides an unprecedented approach to construct all arbitrarily shaped nanoscale molecular structures. ,, The ability to construct robust nanostructures that can also respond to cues is one of the main advantages of DNA nanostructures for biosensing. , Compared to ssDNA probes or duplex probes, the DNA nanostructure-based probes show powerful capability of engineering sensing interfaces such as an ordered and upright orientation and spatial segregation of neighboring probes . These traits contribute to the improved target accessibility .…”

“…3,606,607 The ability to construct robust nanostructures that can also respond to cues is one of the main advantages of DNA nanostructures for biosensing. 608,609 Compared to ssDNA probes or duplex probes, the DNA nanostructure-based probes show powerful capability of engineering sensing interfaces such as an ordered and upright orientation and spatial segregation of neighboring probes. 610 These traits contribute to the improved target accessibility.…”

Intracellular Logic Computation with Framework Nucleic Acid‐Based Circuits for mRNA Imaging†

“…As illustrated in Figure 1, FNAs are designed and used as scaffolds for gates or inputs (Input A or Input B), and such rational design can ensure delivery of FNA‐based circuits into cells without aid of transfection reagents due to FNAs with prominent cellular permeability. [ 11 ] Moreover, the FNA‐based circuits can be suitable for four‐way strand exchange by designing the forked toehold domains at end of pendant duplex DNA. As a result of their predominately double‐stranded nature of components, such circuits can minimize crosstalk with other nucleic acids in complex environments, [ 6b,12 ] which facilitates FNA‐based circuits to work reliably in living cells.…”

Dual-Wavelength Electrochemiluminescence Ratiometric Biosensor for NF-κB p50 Detection with Dimethylthiodiaminoterephthalate Fluorophore and Self-Assembled DNA Tetrahedron Nanostructures Probe

“…The development of DNA nanotechnology not only enables DNA structures to be highly predictable and programmable with extremely precise size and well-defined geometry characteristics, but also realizes the functional requirements such as the detection of pH, O 2 •– , miRNA, and DNA methylation when modified with small molecules. − Among miscellaneous DNA nano architectures, three-dimensional (3D) DNA tetrahedron nanostructures (DTNs) synthesized by the self-assembly of four single strands of DNA attract people’s widespread concern for its high structural stiffness . DTNs with the characteristics of simple synthesis and predictable dimensions will reduce the crowdedness, uneven distribution, and cross-reactivity of single- or double-stranded probes on the surface of electrodes, thereby, improving the biorecognition pathway and lessening the nonspecific absorption. − The vertex of DTNs can be modified by various functional biomolecules or special binding nucleic acid sequences to realize the expansion from traditional 1D and 2D DNA probes to 3D multiple probes. − …”