Pub Date : 2025-11-28DOI: 10.1038/s41557-025-02004-6
Gabriel C. Fonseca, Jazmine O. Cardenas, Angela M Yu
RNA sensors are challenging to design but hold potential for impactful diagnostics. Now, a multi-faceted approach leverages crowdsourcing and computational automation to enable the design of compact RNA-based sensors, shown here for active tuberculosis diagnostics.
{"title":"Engineered RNA sensors for tuberculosis detection","authors":"Gabriel C. Fonseca, Jazmine O. Cardenas, Angela M Yu","doi":"10.1038/s41557-025-02004-6","DOIUrl":"10.1038/s41557-025-02004-6","url":null,"abstract":"RNA sensors are challenging to design but hold potential for impactful diagnostics. Now, a multi-faceted approach leverages crowdsourcing and computational automation to enable the design of compact RNA-based sensors, shown here for active tuberculosis diagnostics.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 12","pages":"1806-1808"},"PeriodicalIF":20.2,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1038/s41557-025-02007-3
Shaozheng Yin, Rui Zhang, Ruihao Zhou, N. Sanjeeva Murthy, Lu Wang, Yuwei Gu
Controlling the rate at which polymers break down is essential for developing sustainable materials. Conventional approaches—which rely on introducing labile and cleavable bonds—often face an inherent trade-off between stability and ease of deconstruction. Inspired by self-deconstruction mechanisms in biomacromolecules, we leverage conformational preorganization of neighbouring groups to modulate and expedite polymer self-deconstruction. Here we show that precise spatial alignment of nucleophilic groups relative to labile bonds regulates the cleavage kinetics by shifting the conformational ensemble towards reactive geometries. This strategy enables programmable deconstruction of both linear polymers and bulk thermosetting networks under ambient conditions, with rates tunable across several orders of magnitude—without altering the chemical identity of the cleavable bond or compromising the polymers’ physical properties. Furthermore, even distal intramolecular functionalities can be harnessed to dynamically control bond cleavability through metal-induced polymer folding, enabling reversible activation and deactivation of self-deconstruction. This work establishes conformational control as a powerful strategy for fine-tuning polymer deconstruction. Cleavable bonds are a central strategy for polymer deconstruction, but controlling the rate of breakdown remains difficult because it is dictated by intrinsic bond cleavage kinetics. Now it has been shown that bio-inspired conformationally preorganized neighbouring groups enable programmable polymer deconstruction without changing the cleavable bond itself or compromising material properties.
{"title":"Conformational preorganization of neighbouring groups modulates and expedites polymer self-deconstruction","authors":"Shaozheng Yin, Rui Zhang, Ruihao Zhou, N. Sanjeeva Murthy, Lu Wang, Yuwei Gu","doi":"10.1038/s41557-025-02007-3","DOIUrl":"10.1038/s41557-025-02007-3","url":null,"abstract":"Controlling the rate at which polymers break down is essential for developing sustainable materials. Conventional approaches—which rely on introducing labile and cleavable bonds—often face an inherent trade-off between stability and ease of deconstruction. Inspired by self-deconstruction mechanisms in biomacromolecules, we leverage conformational preorganization of neighbouring groups to modulate and expedite polymer self-deconstruction. Here we show that precise spatial alignment of nucleophilic groups relative to labile bonds regulates the cleavage kinetics by shifting the conformational ensemble towards reactive geometries. This strategy enables programmable deconstruction of both linear polymers and bulk thermosetting networks under ambient conditions, with rates tunable across several orders of magnitude—without altering the chemical identity of the cleavable bond or compromising the polymers’ physical properties. Furthermore, even distal intramolecular functionalities can be harnessed to dynamically control bond cleavability through metal-induced polymer folding, enabling reversible activation and deactivation of self-deconstruction. This work establishes conformational control as a powerful strategy for fine-tuning polymer deconstruction. Cleavable bonds are a central strategy for polymer deconstruction, but controlling the rate of breakdown remains difficult because it is dictated by intrinsic bond cleavage kinetics. Now it has been shown that bio-inspired conformationally preorganized neighbouring groups enable programmable polymer deconstruction without changing the cleavable bond itself or compromising material properties.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"407-417"},"PeriodicalIF":20.2,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1038/s41557-025-02003-7
Huaibo Zhao, Dario Filippini, Yiding Chen, Albert Gallego-Gamo, Louise S. Natrajan, Loïc R. E. Pantaine, Ciro Romano, David J. Procter
Motifs related to 1,2-diols and 1,2-amino alcohols are found widely in bioactive natural products, drugs and agrochemicals. These highly sought-after substructures would ideally be constructed by the direct addition of alcohols to the C=C bond of alkenes, both common substrate classes in chemical synthesis. However, their direct union is only possible if one of the pair can be rendered electron-deficient through derivatization; such approaches typically require stoichiometric amounts of strong oxidants and often lack generality. Here we describe a straightforward process in which both simple and complex alcohols can be converted under photocatalytic conditions to the corresponding alkoxy radicals—via the formation of alkoxy sulfonium salts—that react with alkenes en route to 1,2-diol and 1,2-amino-alcohol derivatives. The method can be easily adapted from laboratory to industrial, kilogram scale using a photoflow system. Spectroscopic analysis and control experiments have been used to probe the underpinning mechanism. 1,2-Diols and 1,2-amino alcohols are widely found in bioactive compounds. Now it has been shown that alcohols can be converted, via alkoxy sulfonium salts, to alkoxy radicals that add to alkenes to give 1,2-diol and 1,2-amino-alcohol derivatives. The photocatalytic method can be run on a kilogram scale using a photoflow system.
{"title":"Activation of alcohols as sulfonium salts in the photocatalytic hetero-difunctionalization of alkenes","authors":"Huaibo Zhao, Dario Filippini, Yiding Chen, Albert Gallego-Gamo, Louise S. Natrajan, Loïc R. E. Pantaine, Ciro Romano, David J. Procter","doi":"10.1038/s41557-025-02003-7","DOIUrl":"10.1038/s41557-025-02003-7","url":null,"abstract":"Motifs related to 1,2-diols and 1,2-amino alcohols are found widely in bioactive natural products, drugs and agrochemicals. These highly sought-after substructures would ideally be constructed by the direct addition of alcohols to the C=C bond of alkenes, both common substrate classes in chemical synthesis. However, their direct union is only possible if one of the pair can be rendered electron-deficient through derivatization; such approaches typically require stoichiometric amounts of strong oxidants and often lack generality. Here we describe a straightforward process in which both simple and complex alcohols can be converted under photocatalytic conditions to the corresponding alkoxy radicals—via the formation of alkoxy sulfonium salts—that react with alkenes en route to 1,2-diol and 1,2-amino-alcohol derivatives. The method can be easily adapted from laboratory to industrial, kilogram scale using a photoflow system. Spectroscopic analysis and control experiments have been used to probe the underpinning mechanism. 1,2-Diols and 1,2-amino alcohols are widely found in bioactive compounds. Now it has been shown that alcohols can be converted, via alkoxy sulfonium salts, to alkoxy radicals that add to alkenes to give 1,2-diol and 1,2-amino-alcohol derivatives. The photocatalytic method can be run on a kilogram scale using a photoflow system.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"398-406"},"PeriodicalIF":20.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41557-025-02003-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.1038/s41557-025-01977-8
Ya-Wei Zhou, Enric Ibáñez-Alé, Núria López, Beatriz Roldan Cuenya, Christopher S. Kley
Interfacial hydration layers critically determine energy and chemical conversion processes, notably influencing the kinetics of electrocatalytic reactions. Fundamental mechanisms of reactions such as CO 2 electroreduction and hydrogen evolution remain controversial due to the challenge of in situ deciphering of hydration structures alongside reaction intermediates and products. Here, by using vibrational and electrochemical spectroscopy paired with theory we reveal how carbonates structure interfacial water, affecting CO 2 electroreduction and hydrogen evolution reactions on gold electrocatalysts in bicarbonate electrolytes. High cathodic potentials accelerate hydrogen evolution reactions by rapid proton delivery from ordered interfacial hydration networks, induced by carbonate molecules in equilibrium with their anion radicals. These radicals can serve, in addition to CO 2 , as a carbon source for CO and aldehyde production. Moreover we show water to be the primary proton donor for CO 2 electroreduction and hydrogen evolution reactions, with bicarbonate mostly participating in the Heyrovsky step. Our molecular-level insights are relevant to rationalizing and optimizing electrochemical interfaces.
{"title":"Carbonate anions and radicals induce interfacial water ordering in CO2 electroreduction on gold","authors":"Ya-Wei Zhou, Enric Ibáñez-Alé, Núria López, Beatriz Roldan Cuenya, Christopher S. Kley","doi":"10.1038/s41557-025-01977-8","DOIUrl":"https://doi.org/10.1038/s41557-025-01977-8","url":null,"abstract":"Interfacial hydration layers critically determine energy and chemical conversion processes, notably influencing the kinetics of electrocatalytic reactions. Fundamental mechanisms of reactions such as CO <jats:sub>2</jats:sub> electroreduction and hydrogen evolution remain controversial due to the challenge of in situ deciphering of hydration structures alongside reaction intermediates and products. Here, by using vibrational and electrochemical spectroscopy paired with theory we reveal how carbonates structure interfacial water, affecting CO <jats:sub>2</jats:sub> electroreduction and hydrogen evolution reactions on gold electrocatalysts in bicarbonate electrolytes. High cathodic potentials accelerate hydrogen evolution reactions by rapid proton delivery from ordered interfacial hydration networks, induced by carbonate molecules in equilibrium with their anion radicals. These radicals can serve, in addition to CO <jats:sub>2</jats:sub> , as a carbon source for CO and aldehyde production. Moreover we show water to be the primary proton donor for CO <jats:sub>2</jats:sub> electroreduction and hydrogen evolution reactions, with bicarbonate mostly participating in the Heyrovsky step. Our molecular-level insights are relevant to rationalizing and optimizing electrochemical interfaces.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"136 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1038/s41557-025-02005-5
D. I. Ioannou, J. N. H. Reek
Electrophotocatalysis offers a promising strategy for relatively inert molecules, but designing robust systems has been challenging. Now, heterogeneous polymers, composed of perylenediimide units with flexible linkers, unlock chloroarene reduction and functionalization through closed-shell dianion generation and substrate precomplexation.
{"title":"Heterogeneous polymer designs that bring electricity, light and substrates together","authors":"D. I. Ioannou, J. N. H. Reek","doi":"10.1038/s41557-025-02005-5","DOIUrl":"10.1038/s41557-025-02005-5","url":null,"abstract":"Electrophotocatalysis offers a promising strategy for relatively inert molecules, but designing robust systems has been challenging. Now, heterogeneous polymers, composed of perylenediimide units with flexible linkers, unlock chloroarene reduction and functionalization through closed-shell dianion generation and substrate precomplexation.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 12","pages":"1809-1810"},"PeriodicalIF":20.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1038/s41557-025-01997-4
Zixu Wang, Chengxiang Ding, Yizhen Chen, Mengdi Huang, Dongmin Wang, Lei Xu, Sudip Pan, Shengfa Ye, Gengwen Tan
Isonitriles (R–N≡C), first discovered by Lieke in 1859, are well-established functional molecules in organic and organometallic chemistry. By contrast, the synthesis and investigation of tetrela-isonitriles (R–N≡E, E = Si, Ge, Sn or Pb), their heavier group 14 analogues, remain challenging due to their high reactivity. The characterization of such species has largely relied on spectroscopic data collected at cryogenic temperatures or under gas-phase conditions. Here we report the synthesis and characterization of a germa-isonitrile (Ar–N≡Ge) stabilized by a bulky aryl ligand. This compound, which features a terminal N≡Ge triple bond with a Ge‒N bond length of 1.6395(19) Å, has been characterized through X-ray crystallographic, solid-state ¹⁵N nuclear magnetic resonance spectroscopic and computational studies. The highly polarized N≡Ge moiety exhibits versatile reactivity towards organic substrates and transition metal precursors, underscoring its potential use in synthetic chemistry. The study of tetrela-isonitriles—the heavier group 14 analogues of isonitriles—has largely relied on the investigation of transient species under matrix isolation or gas-phase conditions. Now a germa-isonitrile featuring a terminal N≡Ge triple bond and a pseudo-monocoordinate germanium atom has been isolated in the condensed phase. Its reactivity towards selected organic substrates and transition metal complexes has also been explored.
异腈（R-N≡C）于1859年由李克首次发现，是有机和有机金属化学中公认的功能分子。相比之下，四元异腈（R-N≡E, E = Si, Ge， Sn或Pb）的合成和研究，它们较重的14族类似物，由于其高反应性仍然具有挑战性。这类物质的表征很大程度上依赖于在低温或气相条件下收集的光谱数据。在这里，我们报道了一种由庞大的芳基配体稳定的锗异腈（Ar-N≡Ge）的合成和表征。该化合物以端N≡Ge三键为特征，Ge - N键长为1.6395（19）Å，已通过x射线晶体学、固态¹5 N核磁共振光谱和计算研究对其进行了表征。高度极化的N≡Ge基团对有机底物和过渡金属前体表现出多种反应性，强调了其在合成化学中的潜在用途。四元异腈（四元异腈的重基团14类似物）的研究主要依赖于在基质分离或气相条件下对瞬态物质的研究。现在，在缩合相中分离出了一个末端为N≡Ge三键和伪单配位锗原子的锗-异腈。它对选定的有机底物和过渡金属配合物的反应性也进行了探索。
{"title":"An isolable germa-isonitrile featuring a terminal nitrogen–germanium triple bond","authors":"Zixu Wang, Chengxiang Ding, Yizhen Chen, Mengdi Huang, Dongmin Wang, Lei Xu, Sudip Pan, Shengfa Ye, Gengwen Tan","doi":"10.1038/s41557-025-01997-4","DOIUrl":"10.1038/s41557-025-01997-4","url":null,"abstract":"Isonitriles (R–N≡C), first discovered by Lieke in 1859, are well-established functional molecules in organic and organometallic chemistry. By contrast, the synthesis and investigation of tetrela-isonitriles (R–N≡E, E = Si, Ge, Sn or Pb), their heavier group 14 analogues, remain challenging due to their high reactivity. The characterization of such species has largely relied on spectroscopic data collected at cryogenic temperatures or under gas-phase conditions. Here we report the synthesis and characterization of a germa-isonitrile (Ar–N≡Ge) stabilized by a bulky aryl ligand. This compound, which features a terminal N≡Ge triple bond with a Ge‒N bond length of 1.6395(19) Å, has been characterized through X-ray crystallographic, solid-state ¹⁵N nuclear magnetic resonance spectroscopic and computational studies. The highly polarized N≡Ge moiety exhibits versatile reactivity towards organic substrates and transition metal precursors, underscoring its potential use in synthetic chemistry. The study of tetrela-isonitriles—the heavier group 14 analogues of isonitriles—has largely relied on the investigation of transient species under matrix isolation or gas-phase conditions. Now a germa-isonitrile featuring a terminal N≡Ge triple bond and a pseudo-monocoordinate germanium atom has been isolated in the condensed phase. Its reactivity towards selected organic substrates and transition metal complexes has also been explored.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"356-363"},"PeriodicalIF":20.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-21DOI: 10.1038/s41557-025-02000-w
Xianglin Zhu, Ruijie Deng
Subtle mutations in the genome play key roles in both disease progression and pathogen evolution. Now, a fluorescent aptamer-based RNA switch has been shown to enable rapid and robust detection of single nucleotide mutations.
{"title":"Ultraspecific RNA switches for robust mutation detection","authors":"Xianglin Zhu, Ruijie Deng","doi":"10.1038/s41557-025-02000-w","DOIUrl":"10.1038/s41557-025-02000-w","url":null,"abstract":"Subtle mutations in the genome play key roles in both disease progression and pathogen evolution. Now, a fluorescent aptamer-based RNA switch has been shown to enable rapid and robust detection of single nucleotide mutations.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 12","pages":"1803-1805"},"PeriodicalIF":20.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145560435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-21DOI: 10.1038/s41557-025-01987-6
Electrifying nonaqueous thermocatalytic reactions is challenging. Now, a multiphase approach that uses aqueous electrochemistry to drive a nonaqueous reaction through aqueous–nonaqueous interfacial proton-coupled electron transfer is developed for the production of hydrogen peroxide.
{"title":"Bridging aqueous electrochemistry and non-aqueous chemistry for chemical production","authors":"","doi":"10.1038/s41557-025-01987-6","DOIUrl":"10.1038/s41557-025-01987-6","url":null,"abstract":"Electrifying nonaqueous thermocatalytic reactions is challenging. Now, a multiphase approach that uses aqueous electrochemistry to drive a nonaqueous reaction through aqueous–nonaqueous interfacial proton-coupled electron transfer is developed for the production of hydrogen peroxide.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 12","pages":"1815-1816"},"PeriodicalIF":20.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-21DOI: 10.1038/s41557-025-02006-4
Lukas Palatinus
Determining the enantiomorphic excess in chiral solids remains a difficult task, yet it is crucial for the characterization of materials such as chiral catalysts. Now, a combination of 3D electron diffraction, dynamical diffraction calculations, and automated processing enables the quantification of enantiomorphs in a fast and reliable manner.
{"title":"Determining chirality in crystalline powders through 3D electron diffraction","authors":"Lukas Palatinus","doi":"10.1038/s41557-025-02006-4","DOIUrl":"10.1038/s41557-025-02006-4","url":null,"abstract":"Determining the enantiomorphic excess in chiral solids remains a difficult task, yet it is crucial for the characterization of materials such as chiral catalysts. Now, a combination of 3D electron diffraction, dynamical diffraction calculations, and automated processing enables the quantification of enantiomorphs in a fast and reliable manner.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 12","pages":"1813-1814"},"PeriodicalIF":20.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145560427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-21DOI: 10.1038/s41557-025-01995-6
Zhaoqing Yan, Yudan Li, Amit Eshed, Kaiyue Wu, Zachary M. Ticktin, Vel Murugan, Efrem S. Lim, Fan Hong, Alexander A. Green
The ability to detect single nucleotide polymorphisms (SNPs) is critical for identifying genetic disorders, assessing pathogen drug resistance and preventing infection transmission. Achieving a delicate balance across sequence-specific recognition, RNA structural stability and functional efficacy based on SNP-induced changes is crucial for precise genotyping using RNA-based probes. Here we report on in silico-designed aptamer-based RNA switches, referred to as ‘fast aptamer-based reporters for single-nucleotide-specific identification and genotyping through hybridization’ (FARSIGHTs), that enable rapid, low-leakage and multiplexed identification of virtually any target sequence with single-nucleotide specificity. Activation of the FARSIGHT probe can occur in as little as 5 min, separate from upstream amplification. Coupling FARSIGHTs with isothermal amplification enables the robust detection of single nucleotide mutations at attomolar concentrations through strong fluorescence output. We have demonstrated this by distinguishing the SARS-CoV-2 Omicron variant from Alpha, Beta and Gamma with 100% accuracy in RNA from clinical saliva samples. FARSIGHTs can be easily reprogrammed for genotyping emerging pathogens, with potential uses in point-of-care infectious disease monitoring and personalized healthcare applications. The robust detection of single nucleotide variants (SNVs) remains a key challenge for rapid and multiplexed diagnostics. Now it is shown that FARSIGHT, a computationally designed aptamer-based RNA switch, achieves rapid, enzyme-free genotyping via domino-like coupled strand-displacement reactions. These systems provide attomolar sensitivity when coupled with isothermal amplification, multiplexed SNV discrimination and lateral flow readout.
{"title":"Programmable fluorescent aptamer-based RNA switches for rapid identification of point mutations","authors":"Zhaoqing Yan, Yudan Li, Amit Eshed, Kaiyue Wu, Zachary M. Ticktin, Vel Murugan, Efrem S. Lim, Fan Hong, Alexander A. Green","doi":"10.1038/s41557-025-01995-6","DOIUrl":"10.1038/s41557-025-01995-6","url":null,"abstract":"The ability to detect single nucleotide polymorphisms (SNPs) is critical for identifying genetic disorders, assessing pathogen drug resistance and preventing infection transmission. Achieving a delicate balance across sequence-specific recognition, RNA structural stability and functional efficacy based on SNP-induced changes is crucial for precise genotyping using RNA-based probes. Here we report on in silico-designed aptamer-based RNA switches, referred to as ‘fast aptamer-based reporters for single-nucleotide-specific identification and genotyping through hybridization’ (FARSIGHTs), that enable rapid, low-leakage and multiplexed identification of virtually any target sequence with single-nucleotide specificity. Activation of the FARSIGHT probe can occur in as little as 5 min, separate from upstream amplification. Coupling FARSIGHTs with isothermal amplification enables the robust detection of single nucleotide mutations at attomolar concentrations through strong fluorescence output. We have demonstrated this by distinguishing the SARS-CoV-2 Omicron variant from Alpha, Beta and Gamma with 100% accuracy in RNA from clinical saliva samples. FARSIGHTs can be easily reprogrammed for genotyping emerging pathogens, with potential uses in point-of-care infectious disease monitoring and personalized healthcare applications. The robust detection of single nucleotide variants (SNVs) remains a key challenge for rapid and multiplexed diagnostics. Now it is shown that FARSIGHT, a computationally designed aptamer-based RNA switch, achieves rapid, enzyme-free genotyping via domino-like coupled strand-displacement reactions. These systems provide attomolar sensitivity when coupled with isothermal amplification, multiplexed SNV discrimination and lateral flow readout.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 12","pages":"1826-1838"},"PeriodicalIF":20.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145560430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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