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 size-selective 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.
Highlights
Size selectivity is an important mechanism for molecular recognition based on the size difference between targets and non-targets
Larger molecules are prohibited from contacting with inner active catalytic sites, while smaller target molecules are able to enter the pores to participate in chemical reaction (Fig. 1a)
DNAzymes represent one common kind of functional nucleic acid that was first employed as a model to demonstrate the concept of sizeselective recognition based on a cavity-tunable framework nucleic acids
Summary
Size selectivity is an important mechanism for molecular recognition based on the size difference between targets and non-targets. The rational design of an artificial size-selective molecular recognition system for biological targets in living cells remains challenging, because of the difficulty in the precise and site-specific functionalization of molecular recognition elements in a precise framework with nanometer precision. Combining the advantage of these two kinds of nucleic acids, we develop a DNA molecular sieve for size-selective recognition through the site-specific encapsulation of functional nucleic acids in cavitytunable framework nucleic acids in an efficient and controlled manner. Based on this strategy, the DNA molecular sieve can protect DNAzyme from nuclease digestion and non-specific protein absorption, and exhibit the versatility for other a Traditional molecular sieve. The DNA molecular sieve can achieve size-selectivity biosensing, which is capable of distinguishing mature microRNA from precursor microRNA
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