Controllable DNA hybridization by host–guest complexation-mediated ligand invasion

Xiao, Lin; Wang, Liangliang; Wu, Chaoqun; Li, Han; Zhang, Qiulong; Wang, Yang; Xu, Liang

doi:10.1038/s41467-022-33738-3

Cited by 12 publications

(12 citation statements)

References 60 publications

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“…After examining these biochemical features of the crosslinked HHR, we then applied this chemically modified ribozyme to human cells to check its performance as a genesilencing tool. In order to explicitly monitor its efficiency, we first utilized this HHR to target the destabilized EGFP gene in the lentivirus-infected HEK293T cell line (HEK293T-d2EGFP), 45 so that the RNAi effects could be timely and directly observed from the changes of fluorescence signals (Figure 5A). Slightly different from the cross-linked HHR constructed for biochemical assays, we prolonged the length of Stem III (∼10 bp, depending on the sequence context) to ensure its stable binding against the RNA substrate under the cellular conditions (Figure 5B).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Chemically Cross-Linked Hammerhead Ribozyme as an Efficient RNA Interference Tool

Wang,

Wu,

Zhang

et al. 2024

J. Am. Chem. Soc.

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RNA-cleaving ribozymes are promising candidates as general tools of RNA interference (RNAi) in gene manipulation. However, compared with other RNA systems, such as siRNA and CRISPR technologies, the ribozyme tools are still far from broad applications on RNAi due to their poor performance in the cellular context. In this work, we report an efficient RNAi tool based on chemically modified hammerhead ribozyme (HHR). By the introduction of an intramolecular linkage into the minimal HHR to reconstruct the distal interaction within the tertiary ribozyme structure, this cross-linked HHR exhibits efficient RNA substrate cleavage activities with almost no sequence constraint. Cellular experiments suggest that both exogenous and endogenous RNA expression can be dramatically knocked down by this HHR tool with levels comparable to those of siRNA. Unlike the widely applied protein-recruiting RNA systems (siRNA and CRISPR), this ribozyme tool functions solely on RNA itself with great simplicity, which may provide a new approach for gene manipulation in both fundamental and translational studies.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Chemically Cross-Linked Hammerhead Ribozyme as an Efficient RNA Interference Tool

Wang,

Wu,

Zhang

et al. 2024

J. Am. Chem. Soc.

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“…Although the present study developed guest-modified adenosine derivatives, Xiao et al reported the formation of a re-versible base pair via host-guest interaction. 48 They attached guest moieties on the amino group of adenosine and cytidine through the C1 linker and demonstrated the reversible duplex formation using CB [7]. However, their nucleosides (e.g., A AD ) inherently destabilized the duplex regardless of the host-guest interaction (Figure S14) and exhibited a low affinity for complexation with CB [7].…”

Section: Structural Refinement To Tune the Kinetics Of The Reversible...mentioning

confidence: 99%

Reversible control of gene expression by guest-modified adenosines in a cell-free system via host–guest interaction

Okamura,

Yao,

Nagatsugi

2024

Preprint

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Gene expression technology has become an indispensable tool for elucidating biological processes and developing bio-technology. Cell-free gene expression (CFE) systems offer a fundamental platform for gene expression-based technology, in which the reversible and programmable control of transcription can expand its use in synthetic biology and medicine. This study shows that CFE can be controlled via the host–guest interaction of cucurbit[7]uril (CB[7]) with N6-guest-modified adenosines. These adenosine derivatives were conveniently incorporated into the DNA strand by a post-synthetic approach and formed a selective and stable base pair with complementary thymidine in DNA. Meanwhile, alternate addition of CB[7] and the exchanging guest molecule induced the reversible formation of a duplex structure through the formation and dissociation of a bulky complex on DNA. The kinetics of the reversibility were fine-tuned by changing the size of the modified guest moieties. When incorporated into a specific region of the T7 promoter sequence, the guest-modified adenosines enabled the tight and reversible control of in vitro transcription and protein expression in the CFE system. The present study marks the first utility of the host-guest interaction for the gene expression control in the CFE system, opening new avenues for developing DNA-based technology, particularly for precise gene therapy and DNA nano-technology.

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“…Supramolecular polymeric networks (SPNs) are polymeric networks constructed by both covalent and noncovalent interactions. , SPN-based materials combine the advantages of both covalent and noncovalent polymers through efficient functionalization, and they have a wide range of applications. − The dynamic noncovalent supramolecular interactions in the SPNs endow the corresponding materials with high processability and excellent stimulus-responsiveness. − Among the numerous supramolecular interactions, the outstanding selectivity and tunability make the host–guest interactions one of the widely studied topics in supramolecular chemistry. − There are many macrocycle-based host–guest systems, such as crown ethers, − cyclodextrins, , cucurbit[n]urils, , pillararenes, , calixarenes, heteracalixaromatics, corona[n]arenes, and beltarenes . Among them, crown ethers, the first generation of macrocyclic hosts, play a key role in the development of host–guest and supramolecular chemistry.…”

Section: Introductionmentioning

confidence: 99%

Single-Molecule Study Reveals Ion-Dependent Conformational Change and Nanomechanical Property of Crown Ether-Based Polymer

Liu,

Yao,

Sun

et al. 2024

Macromolecules

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The host−guest recognition of crown ethers and alkali metal ions plays a key role in many functional systems. The understanding of the static conformation of the crown ether ring and guest ion is steadily growing, but little is known about the dynamic response of the complex structure when the crown ether ring is deformed. In this study, we successfully monitored the conformational changes of the host−guest complex formed by poly(dibenzo-18-crown-6) and metal ions through single-molecule force spectroscopy and constrained geometry simulated external force calculations. A distinctive shoulder-like force plateau can be observed on the force−extension curve, which depends on both the cation and anion species. Quantum chemical calculations revealed that during the conformation change, the number of coordination bonds between the oxygen atoms on the ring and K + ions were dynamically changed from six to four with an intermediate bond number of two, and K + was gradually squeezed out of the center of the crown ether ring. In addition, the size of the alkali metal ions was found to greatly affect its deformation pathway. This study deepened our understanding of crown ether-based host−guest interactions in a brand-new vision. And, it is useful for tuning the properties of crown ether-based functional materials because the DB18C6 unit can be easily incorporated into the network of polymer materials. Furthermore, such a method can be used to explore and tune the host−guest interactions in other macrocyclebased systems.

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Controllable DNA hybridization by host–guest complexation-mediated ligand invasion

Cited by 12 publications

References 60 publications

Chemically Cross-Linked Hammerhead Ribozyme as an Efficient RNA Interference Tool

Chemically Cross-Linked Hammerhead Ribozyme as an Efficient RNA Interference Tool

Reversible control of gene expression by guest-modified adenosines in a cell-free system via host–guest interaction

Single-Molecule Study Reveals Ion-Dependent Conformational Change and Nanomechanical Property of Crown Ether-Based Polymer

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