Size-selective molecular recognition based on a confined DNA molecular sieve using cavity-tunable framework nucleic acids

Abstract

Size selectivity is an important mechanism for molecular recognition based on the size difference between targets and non-targets. However, rational design of an artificial sizeselective molecular recognition system for biological targets in living cells remains challenging. Herein, we construct a DNA molecular sieve for size-selective molecular recognition to improve the biosensing selectivity in living cells. The system consists of functional nucleic acid probes (e.g., DNAzymes, aptamers and molecular beacons) encapsulated into the inner cavity of framework nucleic acid. Thus, small target molecules are able to enter the cavity for efficient molecular recognition, while large molecules are prohibited. The system not only effectively protect probes from nuclease degradation and nonspecific proteins binding, but also successfully realize size-selective discrimination between mature microRNA and precursor microRNA in living cells. Therefore, the DNA molecular sieve provides a simple, general, efficient and controllable approach for size-selective molecular recognition in biomedical studies and clinical diagnoses.

Construction of nanocarriers based on nucleic acids and their applications in nanobiology delivery systems

“…Nucleic acid probes were encapsulated in the internal cavity of the backbone nucleic acid. Small target molecules could enter the cavity for effective molecular recognition, while large molecules could not [ 78 ] (Fig. 5 b).…”

“…NCNAs are divided into DNA nanocarriers, RNA nanocarriers and DNA/RNA hybrid nanocarriers. These nanostructures are constructed by methods such as self-assembly and combination with nanoparticles, including DNA nanocage [ 78 ], DNA tetrahedron [ 49 ], Se/Ru/siRNA nanomicrotubule [ 67 ], FA/MNP/RNA nanoflower [ 69 ] and Ge-containing nanogel [ 48 ]. DNA nanocage reprinted with permission from ref.…”

DNA nanostructure-based nucleic acid probes: construction and biological applications

“…In addition to speeding up the reaction rate, DNA cubes can also be used for molecular screening. Tan et al 77 reported a DNA cube with a cavity-tunable nucleic acid chamber for size-selective molecular recognition. The proposed system consists of functional nucleic acid probes (such as DNAzymes, aptamers, and molecular beacons) which are wrapped in the inner cavity of the DNA cube.…”

DNA‐Based Architectures for in situ Target Biomolecule Analysis in Confined Nano‐space†

“…Benefiting from the different length of mature miRNAs (19—23 nt) and their precursors (60—70 nt), [ 28 ] Tan and co‐workers presented a size‐selective molecular device for sorting two types of miRNA. [ 29 ] By defining the shape of the nanocages, large molecules were forbidden to enter the cavity, while small targets could contact with the interior to achieve efficient molecular recognition (Figure 1D).…”