Engineering Cell‐Surface Receptors with DNA Nanotechnology for Cell Manipulation

Fan, Jiahui; Wang, Hong‐Hui; Xie, Shiyi; Wang, Miao; Nie, Zhou

doi:10.1002/cbic.201900315

Cited by 41 publications

(29 citation statements)

References 95 publications

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“…Notably, the programmable modular design endows the DNA robot with excellent versatility. For instance, the integrated power module can be replaced by other DNAzyme catalytic modules with distinct cofactors, allowing for selective cell manipulation in responding towards a wide range of specific molecular cues [4f, 18e,f] . In this study, we have achieved orthogonal regulation of the target cells with the robots responding to ion (Zn 2+ ) or amino acid (histidine).…”

Section: Discussionmentioning

confidence: 99%

A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility

Gao

Cao

et al. 2021

Angew Chem Int Ed

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Synthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self‐propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane‐floating cell‐surface receptors in a stochastic manner and simultaneously trigger the receptor‐dimerization to activate downstream signaling for cell motility. The cell membrane‐associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell‐driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution.

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Section: Discussionmentioning

confidence: 99%

A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility

Gao

Cao

et al. 2021

Angew Chem Int Ed

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“…Meanwhile, intensive efforts have been made by chemical and biomedical communities to develop alternative strategies for cell-surface engineering [6]. DNA, taking advantage of easy synthesis, convenient modification, high programmability, and good biocompatibility, has become one of the most promising materials in this regard [7][8][9][10]. In addition to being the carrier of genetic information, DNA, with specific biological and chemical functions, carrier of genetic information, DNA, with specific biological and chemical functions, including aptamers, DNAzyme, and molecular beacons, has been developed and attracted a broad interest for both biological and chemical research [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

DNA-Based Molecular Engineering of the Cell Membrane

Wang

Sun

et al. 2022

Membranes

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The cell membrane serves as a barrier and gatekeeper to regulate the cellular transportation of substances and information. It plays a significant role in protecting the cell from the extracellular environment, maintaining intracellular homeostasis, and regulating cellular function and behaviors. The capability to engineer the cell membrane with functional modules that enable dynamic monitoring and manipulating the cell-surface microenvironment would be critical for studying molecular mechanisms underlying various biological processes. To meet this goal, DNA, with intrinsic advantages of high versatility, programmability, and biocompatibility, has gained intense attention as a molecular tool for cell-surface engineering. The past three decades have witnessed the rapid advances of diverse nucleic acid materials, including functional nucleic acids (FNAs), dynamic DNA circuits, and exquisite DNA nanostructures. In this mini review, we have summarized the recent progress of DNA technology for cell membrane engineering, particularly focused on their applications for molecular sensing and imaging, precise cell identification, receptor activity regulation, and artificial membrane structures. Furthermore, we discussed the challenge and outlook on using nucleic acid materials in this specific research area.

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“…DNA has also emerged as a preferred chemical material with designable, predictable and programmable features to engage molecular devices to non‐genetically modulate protein activity [13] . Recent advances in DNA nanotechnology and functional nucleic acids have provided three applicable engineering modules: [14] (i) the recognition module for specific and non‐covalent binding with a protein through its aptamer; [15] (ii) the dynamic control module for protein activity regulation using reconfigurable DNA assembly; [16] and (iii) the biocomputing module with logic gate function based on DNA‐based chemical reaction networks (CRNs) [17] . Aptamers are chemically synthesized single‐stranded oligonucleotides that fold and bind to selected molecular targets as “chemical antibodies”.…”

Section: Introductionmentioning

confidence: 99%

Scan and Unlock: A Programmable DNA Molecular Automaton for Cell‐Selective Activation of Ligand‐Based Signaling

et al. 2021

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Selective modulation of ligand–receptor interaction is essential in targeted therapy. In this study, we design an intelligent “scan and unlock” DNA automaton (SUDA) system to equip a native protein‐ligand with cell‐identity recognition and receptor‐mediated signaling in a cell‐type‐specific manner. Using embedded DNA‐based chemical reaction networks (CRNs) on the cell surface, SUDA scans and evaluates molecular profiles of cell‐surface proteins via Boolean logic circuits. Therefore, it achieves cell‐specific signal modulation by quickly unlocking the protein‐ligand in proximity to the target cell‐surface to activate its cognate receptor. As a proof of concept, we non‐genetically engineered hepatic growth factor (HGF) with distinct logic SUDAs to elicit target cell‐specific HGF signaling and wound healing behaviors in multiple heterogeneous cell types. Furthermore, the versatility of the SUDA strategy was shown by engineering tumor necrotic factor‐α (TNFα) to induce programmed cell death of target cell subpopulations through cell‐specific modulation of TNFR1 signaling.

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Engineering Cell‐Surface Receptors with DNA Nanotechnology for Cell Manipulation

Cited by 41 publications

References 95 publications

A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility

A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility

DNA-Based Molecular Engineering of the Cell Membrane

Scan and Unlock: A Programmable DNA Molecular Automaton for Cell‐Selective Activation of Ligand‐Based Signaling

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