Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, 410082, Changsha, China.
Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, The Cancer Hospital of the University of Chinese Academy of Sciences, 310022, Hangzhou, Zhejiang, China.
Nat Commun. 2020 Mar 23;11(1):1518. doi: 10.1038/s41467-020-15297-7.
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.
尺寸选择性是一种基于目标与非目标之间大小差异的分子识别的重要机制。然而，合理设计用于在活细胞中对生物靶标进行尺寸选择性分子识别的人工尺寸选择性分子识别系统仍然具有挑战性。在此，我们构建了一种 DNA 分子筛，用于尺寸选择性分子识别，以提高活细胞中的生物传感选择性。该系统由封装在框架核酸内腔中的功能核酸探针（例如 DNA 酶、适体和分子信标）组成。因此，小分子靶标能够进入腔中进行有效的分子识别，而大分子则被禁止。该系统不仅能有效地保护探针免受核酸酶降解和非特异性蛋白质结合的影响，而且还能成功地在活细胞中实现成熟 microRNA 和前体 microRNA 之间的尺寸选择性区分。因此，DNA 分子筛为生物医学研究和临床诊断中的尺寸选择性分子识别提供了一种简单、通用、高效和可控的方法。
