Pub Date : 2024-08-08DOI: 10.1038/s41565-024-01739-6
A DNA origami nanocompartment is designed to trap an unfoldase machine in a unidirectional orientation. This trapping provides a gateway mechanism for substrate recruitment and translocation to a downstream compartment that hosts a protease. Kinetics and proteomics data demonstrate that the physical connection of the DNA-based modules improves the global performance of the chimera and reduces off-target reactions.
DNA 折纸纳米隔室的设计目的是以单向方向捕获折叠酶机器。这种捕获为底物招募和转运到承载蛋白酶的下游区室提供了一个网关机制。动力学和蛋白质组学数据表明，基于 DNA 的模块的物理连接提高了嵌合体的整体性能，并减少了脱靶反应。
{"title":"Engineering modular enzymes using DNA origami","authors":"","doi":"10.1038/s41565-024-01739-6","DOIUrl":"10.1038/s41565-024-01739-6","url":null,"abstract":"A DNA origami nanocompartment is designed to trap an unfoldase machine in a unidirectional orientation. This trapping provides a gateway mechanism for substrate recruitment and translocation to a downstream compartment that hosts a protease. Kinetics and proteomics data demonstrate that the physical connection of the DNA-based modules improves the global performance of the chimera and reduces off-target reactions.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 10","pages":"1440-1441"},"PeriodicalIF":38.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO4 nanocatalyst, dubbed ‘artificial metabzyme’. It showcases dual active centres, namely, Fe2+ and tetrahedral Mo4+, that mirror the characteristic architecture of the archetypal metabolic enzyme xanthine oxidoreductase. Employing spatially dynamic metabolomics in conjunction with the assessments of tumour-associated metabolites, we demonstrate that FeMoO4 metabzyme catalyses the metabolic conversion of tumour-abundant xanthine into uric acid. Subsequent metabolic adjustments orchestrate crosstalk with immune cells, suggesting a potential therapeutic pathway for cancer. Our study introduces an innovative paradigm in cancer therapy, where tumour cells are metabolically reprogrammed to autonomously modulate and directly interface with immune cells through the intervention of an artificial metabzyme, for tumour-cell-specific metabolic therapy. A metabolic-enzyme-like nanocatalyst is reported, dubbed ‘artificial metabzyme’. Tumour cells can be metabolically reprogrammed to autonomously modulate and interact with immune cells, facilitating tumour-cell-specific metabolic therapy.
{"title":"An artificial metabzyme for tumour-cell-specific metabolic therapy","authors":"Xi Hu, Bo Zhang, Miao Zhang, Wenshi Liang, Bangzhen Hong, Zhiyuan Ma, Jianpeng Sheng, Tianqi Liu, Shengfei Yang, Zeyu Liang, Jichao Zhang, Chunhai Fan, Fangyuan Li, Daishun Ling","doi":"10.1038/s41565-024-01733-y","DOIUrl":"10.1038/s41565-024-01733-y","url":null,"abstract":"Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO4 nanocatalyst, dubbed ‘artificial metabzyme’. It showcases dual active centres, namely, Fe2+ and tetrahedral Mo4+, that mirror the characteristic architecture of the archetypal metabolic enzyme xanthine oxidoreductase. Employing spatially dynamic metabolomics in conjunction with the assessments of tumour-associated metabolites, we demonstrate that FeMoO4 metabzyme catalyses the metabolic conversion of tumour-abundant xanthine into uric acid. Subsequent metabolic adjustments orchestrate crosstalk with immune cells, suggesting a potential therapeutic pathway for cancer. Our study introduces an innovative paradigm in cancer therapy, where tumour cells are metabolically reprogrammed to autonomously modulate and directly interface with immune cells through the intervention of an artificial metabzyme, for tumour-cell-specific metabolic therapy. A metabolic-enzyme-like nanocatalyst is reported, dubbed ‘artificial metabzyme’. Tumour cells can be metabolically reprogrammed to autonomously modulate and interact with immune cells, facilitating tumour-cell-specific metabolic therapy.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 11","pages":"1712-1722"},"PeriodicalIF":38.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1038/s41565-024-01723-0
Yuesong Hu, Jhordan Rogers, Yuxin Duan, Arventh Velusamy, Steven Narum, Sarah Al Abdullatif, Khalid Salaita
The T cell receptor (TCR) is thought to be a mechanosensor, meaning that it transmits mechanical force to its antigen and leverages the force to amplify the specificity and magnitude of TCR signalling. Although a variety of molecular probes have been proposed to quantify TCR mechanics, these probes are immobilized on hard substrates, and thus fail to reveal fluid TCR–antigen interactions in the physiological context of cell membranes. Here we developed DNA origami tension sensors (DOTS) which bear force sensors on a DNA origami breadboard and allow mapping of TCR mechanotransduction at dynamic intermembrane junctions. We quantified the mechanical forces at fluid TCR–antigen bonds and observed their dependence on cell state, antigen mobility, antigen potency, antigen height and F-actin activity. The programmability of DOTS allows us to tether these to microparticles to mechanically screen antigens in high throughput using flow cytometry. Additionally, DOTS were anchored onto live B cells, allowing quantification of TCR mechanics at immune cell–cell junctions. The authors present nanoscale DNA origami tension sensors tethered to lipid membranes and reveal the magnitude, dynamics and driving mechanisms of molecular forces experienced by immunoreceptors at fluid membrane junctions.
{"title":"Quantifying T cell receptor mechanics at membrane junctions using DNA origami tension sensors","authors":"Yuesong Hu, Jhordan Rogers, Yuxin Duan, Arventh Velusamy, Steven Narum, Sarah Al Abdullatif, Khalid Salaita","doi":"10.1038/s41565-024-01723-0","DOIUrl":"10.1038/s41565-024-01723-0","url":null,"abstract":"The T cell receptor (TCR) is thought to be a mechanosensor, meaning that it transmits mechanical force to its antigen and leverages the force to amplify the specificity and magnitude of TCR signalling. Although a variety of molecular probes have been proposed to quantify TCR mechanics, these probes are immobilized on hard substrates, and thus fail to reveal fluid TCR–antigen interactions in the physiological context of cell membranes. Here we developed DNA origami tension sensors (DOTS) which bear force sensors on a DNA origami breadboard and allow mapping of TCR mechanotransduction at dynamic intermembrane junctions. We quantified the mechanical forces at fluid TCR–antigen bonds and observed their dependence on cell state, antigen mobility, antigen potency, antigen height and F-actin activity. The programmability of DOTS allows us to tether these to microparticles to mechanically screen antigens in high throughput using flow cytometry. Additionally, DOTS were anchored onto live B cells, allowing quantification of TCR mechanics at immune cell–cell junctions. The authors present nanoscale DNA origami tension sensors tethered to lipid membranes and reveal the magnitude, dynamics and driving mechanisms of molecular forces experienced by immunoreceptors at fluid membrane junctions.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 11","pages":"1674-1685"},"PeriodicalIF":38.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1038/s41565-024-01716-z
Qilun Wang, Yaqi Cheng, Hong Bin Yang, Chenliang Su, Bin Liu
Single-atom catalysts (SACs) have attracted considerable research interest owing to their combined merits of homogeneous and heterogeneous catalysts. However, the uniform and isolated active sites of SACs fall short in catalysing complex chemical processes that simultaneously involve multiple intermediates. In this Review, we highlight an emerging class of catalysts with adjacent binary active centres, which is called integrative catalytic pairs (ICPs), showing not only atomic-scale site-to-site electronic interactions but also synergistic catalytic effects. Compared with SACs or their derivative dual-atom catalysts (DACs), multi-interactive intermediates on ICPs can overcome kinetic barriers, adjust reaction pathways and break the universal linear scaling relations as the smallest active units. Starting from this active-site design principle, each single active atom can be considered as a brick to further build integrative catalytic clusters (ICCs) with desirable configurations, towards trimer or even larger multi-atom units depending on the requirement of a given reaction. This Review highlights the definition, functions and potential of integrative catalytic pairs in multi-intermediate reactions, as a forward step relative to single- and dual-atom catalysts.
{"title":"Integrative catalytic pairs for efficient multi-intermediate catalysis","authors":"Qilun Wang, Yaqi Cheng, Hong Bin Yang, Chenliang Su, Bin Liu","doi":"10.1038/s41565-024-01716-z","DOIUrl":"10.1038/s41565-024-01716-z","url":null,"abstract":"Single-atom catalysts (SACs) have attracted considerable research interest owing to their combined merits of homogeneous and heterogeneous catalysts. However, the uniform and isolated active sites of SACs fall short in catalysing complex chemical processes that simultaneously involve multiple intermediates. In this Review, we highlight an emerging class of catalysts with adjacent binary active centres, which is called integrative catalytic pairs (ICPs), showing not only atomic-scale site-to-site electronic interactions but also synergistic catalytic effects. Compared with SACs or their derivative dual-atom catalysts (DACs), multi-interactive intermediates on ICPs can overcome kinetic barriers, adjust reaction pathways and break the universal linear scaling relations as the smallest active units. Starting from this active-site design principle, each single active atom can be considered as a brick to further build integrative catalytic clusters (ICCs) with desirable configurations, towards trimer or even larger multi-atom units depending on the requirement of a given reaction. This Review highlights the definition, functions and potential of integrative catalytic pairs in multi-intermediate reactions, as a forward step relative to single- and dual-atom catalysts.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 10","pages":"1442-1451"},"PeriodicalIF":38.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1038/s41565-024-01737-8
Lorenzo Orsini, Hanan Herzig Sheinfux, Yandong Li, Seojoo Lee, Gian Marcello Andolina, Orazio Scarlatella, Matteo Ceccanti, Karuppasamy Soundarapandian, Eli Janzen, James H. Edgar, Gennady Shvets, Frank H. L. Koppens
Topological photonics offers the opportunity to control light propagation in a way that is robust from fabrication disorders and imperfections. However, experimental demonstrations have remained on the order of the vacuum wavelength. Theoretical proposals have shown topological edge states that can propagate robustly while embracing deep subwavelength confinement that defies diffraction limits. Here we show the experimental proof of these deep subwavelength topological edge states by implementing periodic modulation of hyperbolic phonon polaritons within a van der Waals heterostructure composed of isotopically pure hexagonal boron nitride flakes on patterned gold films. The topological edge state is confined in a subdiffraction volume of 0.021 µm3, which is four orders of magnitude smaller than the free-space excitation wavelength volume used to probe the system, while maintaining the resonance quality factor above 100. This finding can be directly extended to and hybridized with other van der Waals materials to broadened operational frequency ranges, streamline integration of diverse polaritonic materials, and compatibility with electronic and excitonic systems. A photonic topological edge state, achieved by employing hexagonal boron nitride and patterned gold films, confines light four orders of magnitude below the diffraction limit while preserving a high quality factor.
{"title":"Deep subwavelength topological edge state in a hyperbolic medium","authors":"Lorenzo Orsini, Hanan Herzig Sheinfux, Yandong Li, Seojoo Lee, Gian Marcello Andolina, Orazio Scarlatella, Matteo Ceccanti, Karuppasamy Soundarapandian, Eli Janzen, James H. Edgar, Gennady Shvets, Frank H. L. Koppens","doi":"10.1038/s41565-024-01737-8","DOIUrl":"10.1038/s41565-024-01737-8","url":null,"abstract":"Topological photonics offers the opportunity to control light propagation in a way that is robust from fabrication disorders and imperfections. However, experimental demonstrations have remained on the order of the vacuum wavelength. Theoretical proposals have shown topological edge states that can propagate robustly while embracing deep subwavelength confinement that defies diffraction limits. Here we show the experimental proof of these deep subwavelength topological edge states by implementing periodic modulation of hyperbolic phonon polaritons within a van der Waals heterostructure composed of isotopically pure hexagonal boron nitride flakes on patterned gold films. The topological edge state is confined in a subdiffraction volume of 0.021 µm3, which is four orders of magnitude smaller than the free-space excitation wavelength volume used to probe the system, while maintaining the resonance quality factor above 100. This finding can be directly extended to and hybridized with other van der Waals materials to broadened operational frequency ranges, streamline integration of diverse polaritonic materials, and compatibility with electronic and excitonic systems. A photonic topological edge state, achieved by employing hexagonal boron nitride and patterned gold films, confines light four orders of magnitude below the diffraction limit while preserving a high quality factor.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 10","pages":"1485-1490"},"PeriodicalIF":38.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1038/s41565-024-01731-0
Quantum sensing at the atomic scale has proved challenging. Now, a quantum sensor comprising a molecular spin, which can be addressed by electron spin resonance, attached to the tip of a scanning tunnelling microscope enables the measurement of weak electric and magnetic fields with sub-ångstrom spatial resolution.
{"title":"A molecular spin on a scanning probe tip enables quantum sensing at the atomic scale","authors":"","doi":"10.1038/s41565-024-01731-0","DOIUrl":"10.1038/s41565-024-01731-0","url":null,"abstract":"Quantum sensing at the atomic scale has proved challenging. Now, a quantum sensor comprising a molecular spin, which can be addressed by electron spin resonance, attached to the tip of a scanning tunnelling microscope enables the measurement of weak electric and magnetic fields with sub-ångstrom spatial resolution.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 10","pages":"1438-1439"},"PeriodicalIF":38.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1038/s41565-024-01740-z
David B. Amabilino
Etching supramolecular fibres causes nanoscale motion of an attached bead from the etched end towards the middle of the fibre.
对超分子纤维进行蚀刻会导致附着的珠子从蚀刻端向纤维中部进行纳米级运动。
{"title":"Moving microscopic objects with self-disassembly","authors":"David B. Amabilino","doi":"10.1038/s41565-024-01740-z","DOIUrl":"10.1038/s41565-024-01740-z","url":null,"abstract":"Etching supramolecular fibres causes nanoscale motion of an attached bead from the etched end towards the middle of the fibre.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 10","pages":"1436-1437"},"PeriodicalIF":38.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1038/s41565-024-01727-w
Annelies C. Wauters, Jari F. Scheerstra, Mandy M. T. van Leent, Abraham J. P. Teunissen, Bram Priem, Thijs J. Beldman, Nils Rother, Raphaël Duivenvoorden, Geoffrey Prévot, Jazz Munitz, Yohana C. Toner, Jeroen Deckers, Yuri van Elsas, Patricia Mora-Raimundo, Gal Chen, Sheqouia A. Nauta, Anna Vera D. Verschuur, Arjan W. Griffioen, David P. Schrijver, Tom Anbergen, Yudong Li, Hanglong Wu, Alexander F. Mason, Marleen H. M. E. van Stevendaal, Ewelina Kluza, Richard A. J. Post, Leo A. B. Joosten, Mihai G. Netea, Claudia Calcagno, Zahi A. Fayad, Roy van der Meel, Avi Schroeder, Loai K. E. A. Abdelmohsen, Willem J. M. Mulder, Jan C. M. van Hest
Regulating innate immunity is an emerging approach to improve cancer immunotherapy. Such regulation requires engaging myeloid cells by delivering immunomodulatory compounds to hematopoietic organs, including the spleen. Here we present a polymersome-based nanocarrier with splenic avidity and propensity for red pulp myeloid cell uptake. We characterized the in vivo behaviour of four chemically identical yet topologically different polymersomes by in vivo positron emission tomography imaging and innovative flow and mass cytometry techniques. Upon intravenous administration, relatively large and spherical polymersomes accumulated rapidly in the spleen and efficiently targeted myeloid cells in the splenic red pulp. When loaded with β-glucan, intravenously administered polymersomes significantly reduced tumour growth in a mouse melanoma model. We initiated our nanotherapeutic’s clinical translation with a biodistribution study in non-human primates, which revealed that the platform’s splenic avidity is preserved across species. Delivering immunomodulatory compounds to myeloid cells can activate innate immunity for cancer immunotherapy. Here the authors design a polymersome-based nanocarrier for delivering β-glucan to red pulp myeloid cells in the spleen and show that their strategy achieves tumour growth reduction in a melanoma model.
{"title":"Polymersomes with splenic avidity target red pulp myeloid cells for cancer immunotherapy","authors":"Annelies C. Wauters, Jari F. Scheerstra, Mandy M. T. van Leent, Abraham J. P. Teunissen, Bram Priem, Thijs J. Beldman, Nils Rother, Raphaël Duivenvoorden, Geoffrey Prévot, Jazz Munitz, Yohana C. Toner, Jeroen Deckers, Yuri van Elsas, Patricia Mora-Raimundo, Gal Chen, Sheqouia A. Nauta, Anna Vera D. Verschuur, Arjan W. Griffioen, David P. Schrijver, Tom Anbergen, Yudong Li, Hanglong Wu, Alexander F. Mason, Marleen H. M. E. van Stevendaal, Ewelina Kluza, Richard A. J. Post, Leo A. B. Joosten, Mihai G. Netea, Claudia Calcagno, Zahi A. Fayad, Roy van der Meel, Avi Schroeder, Loai K. E. A. Abdelmohsen, Willem J. M. Mulder, Jan C. M. van Hest","doi":"10.1038/s41565-024-01727-w","DOIUrl":"10.1038/s41565-024-01727-w","url":null,"abstract":"Regulating innate immunity is an emerging approach to improve cancer immunotherapy. Such regulation requires engaging myeloid cells by delivering immunomodulatory compounds to hematopoietic organs, including the spleen. Here we present a polymersome-based nanocarrier with splenic avidity and propensity for red pulp myeloid cell uptake. We characterized the in vivo behaviour of four chemically identical yet topologically different polymersomes by in vivo positron emission tomography imaging and innovative flow and mass cytometry techniques. Upon intravenous administration, relatively large and spherical polymersomes accumulated rapidly in the spleen and efficiently targeted myeloid cells in the splenic red pulp. When loaded with β-glucan, intravenously administered polymersomes significantly reduced tumour growth in a mouse melanoma model. We initiated our nanotherapeutic’s clinical translation with a biodistribution study in non-human primates, which revealed that the platform’s splenic avidity is preserved across species. Delivering immunomodulatory compounds to myeloid cells can activate innate immunity for cancer immunotherapy. Here the authors design a polymersome-based nanocarrier for delivering β-glucan to red pulp myeloid cells in the spleen and show that their strategy achieves tumour growth reduction in a melanoma model.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 11","pages":"1735-1744"},"PeriodicalIF":38.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41565-024-01727-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-30DOI: 10.1038/s41565-024-01726-x
Giacomo Fabrini, Nada Farag, Sabrina Pia Nuccio, Shiyi Li, Jaimie Marie Stewart, Anli A. Tang, Reece McCoy, Róisín M. Owens, Paul W. K. Rothemund, Elisa Franco, Marco Di Antonio, Lorenzo Di Michele
Condensation of RNA and proteins is central to cellular functions, and the ability to program it would be valuable in synthetic biology and synthetic cell science. Here we introduce a modular platform for engineering synthetic RNA condensates from tailor-made, branched RNA nanostructures that fold and assemble co-transcriptionally. Up to three orthogonal condensates can form simultaneously and selectively accumulate fluorophores through embedded fluorescent light-up aptamers. The RNA condensates can be expressed within synthetic cells to produce membrane-less organelles with a controlled number and relative size, and showing the ability to capture proteins using selective protein-binding aptamers. The affinity between otherwise orthogonal nanostructures can be modulated by introducing dedicated linker constructs, enabling the production of bi-phasic RNA condensates with a prescribed degree of interphase mixing and diverse morphologies. The in situ expression of programmable RNA condensates could underpin the spatial organization of functionalities in both biological and synthetic cells. Controlling RNA and protein condensation is helpful in synthetic biology. Here the authors show programmable assembly of synthetic RNA nanostructures into designer membrane-less organelles that selectively recruit ligands via protein-binding aptamers.
{"title":"Co-transcriptional production of programmable RNA condensates and synthetic organelles","authors":"Giacomo Fabrini, Nada Farag, Sabrina Pia Nuccio, Shiyi Li, Jaimie Marie Stewart, Anli A. Tang, Reece McCoy, Róisín M. Owens, Paul W. K. Rothemund, Elisa Franco, Marco Di Antonio, Lorenzo Di Michele","doi":"10.1038/s41565-024-01726-x","DOIUrl":"10.1038/s41565-024-01726-x","url":null,"abstract":"Condensation of RNA and proteins is central to cellular functions, and the ability to program it would be valuable in synthetic biology and synthetic cell science. Here we introduce a modular platform for engineering synthetic RNA condensates from tailor-made, branched RNA nanostructures that fold and assemble co-transcriptionally. Up to three orthogonal condensates can form simultaneously and selectively accumulate fluorophores through embedded fluorescent light-up aptamers. The RNA condensates can be expressed within synthetic cells to produce membrane-less organelles with a controlled number and relative size, and showing the ability to capture proteins using selective protein-binding aptamers. The affinity between otherwise orthogonal nanostructures can be modulated by introducing dedicated linker constructs, enabling the production of bi-phasic RNA condensates with a prescribed degree of interphase mixing and diverse morphologies. The in situ expression of programmable RNA condensates could underpin the spatial organization of functionalities in both biological and synthetic cells. Controlling RNA and protein condensation is helpful in synthetic biology. Here the authors show programmable assembly of synthetic RNA nanostructures into designer membrane-less organelles that selectively recruit ligands via protein-binding aptamers.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 11","pages":"1665-1673"},"PeriodicalIF":38.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41565-024-01726-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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