Engineering Aptamer with Enhanced Affinity by Triple Helix-Based Terminal Fixation

Zhao, Liye; Qi, Xiaoyan; Yan, Xiaochen; Huang, Yunfei; Liang, Xingguo; Zhang, Liqin; Wang, Sai; Tan, Weihong

doi:10.1021/jacs.9b09292

Cited by 105 publications

(53 citation statements)

References 33 publications

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“…The triple helical structure here serves as a part of the aptamer structure. Our design is also different from those aptasensors that employs triple helical structures to fix the aptamer to improve its structural stability ( 50 ), because the triple helical structure ( 50 ) is used only as an auxiliary element of the aptamer structure. Moreover, there have been efforts to regulate the activity of polymerases and ribozymes ( 51 , 52 ) via the triplex clamp.…”

Section: Discussionmentioning

confidence: 99%

Switching the activity of Taq polymerase using clamp-like triplex aptamer structure

Wang

Chen

et al. 2020

Nucleic Acids Research

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Abstract In nature, allostery is the principal approach for regulating cellular processes and pathways. Inspired by nature, structure-switching aptamer-based nanodevices are widely used in artificial biotechnologies. However, the canonical aptamer structures in the nanodevices usually adopt a duplex form, which limits the flexibility and controllability. Here, a new regulating strategy based on a clamp-like triplex aptamer structure (CLTAS) was proposed for switching DNA polymerase activity via conformational changes. It was demonstrated that the polymerase activity could be regulated by either adjusting structure parameters or dynamic reactions including strand displacement or enzymatic digestion. Compared with the duplex aptamer structure, the CLTAS possesses programmability, excellent affinity and high discrimination efficiency. The CLTAS was successfully applied to distinguish single-base mismatches. The strategy expands the application scope of triplex structures and shows potential in biosensing and programmable nanomachines.

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Section: Discussionmentioning

confidence: 99%

Switching the activity of Taq polymerase using clamp-like triplex aptamer structure

Wang

Chen

et al. 2020

Nucleic Acids Research

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“…Aptamers Aptamers, which are origin from Latin aptus (fit) and Greek meros (part), represent an emerging class of therapeutics. Aptamers, the folded three-dimensional structures of which can recognize various targets including small molecules, peptides, proteins and cells with high affinity are short single-stranded DNA or RNA molecules with 20–100 nucleotides [ 68 , 69 ]. Aptamers are referred to as “synthetic antibodies”, they bind to biological molecules via a very specific manner but not act through sequence-specific complementary paring.…”

Section: Classifications Of the Therapeutic Oligonucleotidesmentioning

confidence: 99%

Delivery of therapeutic oligonucleotides in nanoscale

Zhou

Lin

et al. 2022

Bioactive Materials

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Therapeutic oligonucleotides (TOs) represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily druggable. However, efficiently delivering of TOs to cancer cellular targets is still the biggest challenge in promoting their clinical translations. Emerging as a significant drug delivery vector, nanoparticles (NPs) can not only protect TOs from nuclease degradation and enhance their tumor accumulation, but also can improve the cell uptake efficiency of TOs as well as the following endosomal escape to increase the therapeutic index. Furthermore, targeted and on-demand drug release of TOs can also be approached to minimize the risk of toxicity towards normal tissues using stimuli-responsive NPs. In the past decades, remarkable progresses have been made on the TOs delivery based on various NPs with specific purposes. In this review, we will first give a brief introduction on the basis of TOs as well as the action mechanisms of several typical TOs, and then describe the obstacles that prevent the clinical translation of TOs, followed by a comprehensive overview of the recent progresses on TOs delivery based on several various types of nanocarriers containing lipid-based nanoparticles, polymeric nanoparticles, gold nanoparticles, porous nanoparticles, DNA/RNA nanoassembly, extracellular vesicles, and imaging-guided drug delivery nanoparticles.

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“…Although the aptamer should be flexible to a certain degree to undergo conformational changes upon target binding, the excessive flexibility of the aptamer hampers the folding process, resulting in weak affinity. A strategy that uses a triple helix to fix the terminals can restrict the aptamer flexibility and further increase its binding capacity; 46 the authors engineered the double-helix ends of an anti-lysozyme aptamer to be splinted with a length-optimized strand to form a triple helix. This fixation of the terminal yielded an aptamerbased electrochemical sensor that had an LOD which was 1/180th times as large as that of the non-engineered aptasensor.…”

Section: Materials Advances Reviewmentioning

confidence: 99%

Detection and beyond: challenges and advances in aptamer-based biosensors

Yoo

2020

Mater. Adv.

189

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Engineering Aptamer with Enhanced Affinity by Triple Helix-Based Terminal Fixation

Abstract: The affinity of aptamers relies on their adaptive folding, but the excessive flexibility of the aptamer backbone usually hampers the folding process.

Cited by 105 publications

References 33 publications

Switching the activity of Taq polymerase using clamp-like triplex aptamer structure

Switching the activity of Taq polymerase using clamp-like triplex aptamer structure

Delivery of therapeutic oligonucleotides in nanoscale

Detection and beyond: challenges and advances in aptamer-based biosensors

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