Sasha B. Ebrahimi, Himanshu Bhattacharjee, Sujatha Sonti, Doug Fuerst, Patrick S. Doyle, Yi Lu, Devleena Samanta
{"title":"Engineering considerations for next-generation oligonucleotide therapeutics","authors":"Sasha B. Ebrahimi, Himanshu Bhattacharjee, Sujatha Sonti, Doug Fuerst, Patrick S. Doyle, Yi Lu, Devleena Samanta","doi":"10.1038/s44286-024-00152-z","DOIUrl":"10.1038/s44286-024-00152-z","url":null,"abstract":"Oligonucleotide therapeutics are revolutionizing disease treatment by regulating molecules at the genetic level, offering the possibility of treating conditions that were once considered ‘undruggable’. However, delivering oligonucleotides to tissues beyond the liver remains a key challenge, limiting their clinical applications thus far to niche indications. To achieve broader applicability, extensive biomolecular engineering is necessary to enhance the stability, tissue targetability, pharmacokinetics and pharmacodynamics of these structures. The intricate design of these molecules also demands sophisticated process-engineering techniques. Here we provide a collaborative Perspective from academia and industry on the pivotal role of chemical engineering in expanding the use of therapeutic oligonucleotides to treat a wider range of diseases. We discuss how the interplay between biomolecular and process engineering impacts the developability of next-generation oligonucleotide therapeutics as well as their translation from bench to bedside. Oligonucleotide therapeutics have emerged as a promising alternative to traditional small-molecule and protein-based drugs. This Perspective discusses how chemical engineering can broaden oligonucleotide applications to extrahepatic diseases and enable larger-scale production, ultimately allowing treatment of more prevalent conditions than is currently possible.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 12","pages":"741-750"},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin C. Bui, Eric W. Lees, Andrew K. Liu, Wei Lun Toh, T. Nathan Stovall, Priyamvada Goyal, Francisco Javier U. Galang, Yogesh Surendranath, Alexis T. Bell, Adam Z. Weber
{"title":"Ion-specific phenomena limit energy recovery in forward-biased bipolar membranes","authors":"Justin C. Bui, Eric W. Lees, Andrew K. Liu, Wei Lun Toh, T. Nathan Stovall, Priyamvada Goyal, Francisco Javier U. Galang, Yogesh Surendranath, Alexis T. Bell, Adam Z. Weber","doi":"10.1038/s44286-024-00154-x","DOIUrl":"10.1038/s44286-024-00154-x","url":null,"abstract":"The ability for bipolar membranes (BPMs) to interconvert voltage and pH makes them attractive materials for use in energy conversion and storage. Reverse-biased BPMs, which use electrical voltage to dissociate water into acid and base, have become increasingly well studied. However, forward-biased BPMs (FB-BPMs), in which voltage is extracted from pH gradients through recombination, require further study. Here physics-based modeling elucidates how the complex coupling of transport and kinetics dictates the performance of FB-BPMs in electrochemical devices. Simulations reveal that the open-circuit potential of FB-BPMs is dictated by the balance of ion recombination and crossover, where recombination of buffering counter-ions attenuates the open-circuit potential. Counter-ion mass-transport limitations and uptake of ionic impurities limit achievable current densities by reducing the applied pH gradient or the available fixed-charge sites that mediate recombination. The model highlights the importance of selective ion management in mitigating energy losses and provides insight into the rational material design of FB-BPMs for energy applications. Forward-biased bipolar membranes (FB-BPMs), which recover potential from pH gradients through ion–ion recombination, show promise for application in sustainable devices. The authors use physics-based modeling to elucidate how ion-specific phenomena dictate performance, reveal how selective ion management can mitigate energy losses and provide insights into the rational design of next-generation FB-BPMs.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 1","pages":"63-76"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44286-024-00154-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Moore, Andrew A. Wong, Brian Giera, Diego I. Oyarzun, Aldair E. Gongora, Tiras Y. Lin, Wenqin Li, Tracie Owens, Du Nguyen, Victoria M. Ehlinger, Aditya Prajapati, Seung Whan Chung, Pratanu Roy, Joshua DeOtte, Nicholas R. Cross, Alvina Aui, Youngsoo Choi, Maxwell Goldman, Hui-Yun Jeong, Congwang Ye, Amitava Sarkar, Eric B. Duoss, Christopher Hahn, Sarah E. Baker
{"title":"Accelerating climate technologies through the science of scale-up","authors":"Thomas Moore, Andrew A. Wong, Brian Giera, Diego I. Oyarzun, Aldair E. Gongora, Tiras Y. Lin, Wenqin Li, Tracie Owens, Du Nguyen, Victoria M. Ehlinger, Aditya Prajapati, Seung Whan Chung, Pratanu Roy, Joshua DeOtte, Nicholas R. Cross, Alvina Aui, Youngsoo Choi, Maxwell Goldman, Hui-Yun Jeong, Congwang Ye, Amitava Sarkar, Eric B. Duoss, Christopher Hahn, Sarah E. Baker","doi":"10.1038/s44286-024-00143-0","DOIUrl":"10.1038/s44286-024-00143-0","url":null,"abstract":"Avoiding the worst effects of climate change depends on our ability to scale and deploy technologies faster than ever before. Scale-up has largely been the domain of industrial research and development teams, but advances in modeling and experimental techniques increasingly allow early-stage researchers to contribute to the process. Here we argue that early assessments of technology market fit and how the physics governing system performance evolves with scale can de-risk technology development and accelerate deployment. We highlight tools and processes that can be used to assess both these factors at an early stage. By bringing together technical risk assessments, scaled physics modeling, data analysis and in situ experimentation within multidisciplinary teams, new technologies can be invented, developed and deployed on a shorter timetable with greater probability of success. This Perspective argues that early assessments of technology-market fit, as well as how the physics governing system performance evolves with scale, can de-risk technology development and accelerate deployment. The authors highlight tools and processes that can be used to assess both these factors at an early stage.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 12","pages":"731-740"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kiana Amini, Thomas Cochard, Yan Jing, Jordan D. Sosa, Dawei Xi, Maia Alberts, Michael S. Emanuel, Emily F. Kerr, Roy G. Gordon, Michael J. Aziz
{"title":"In situ techniques for aqueous quinone-mediated electrochemical carbon capture and release","authors":"Kiana Amini, Thomas Cochard, Yan Jing, Jordan D. Sosa, Dawei Xi, Maia Alberts, Michael S. Emanuel, Emily F. Kerr, Roy G. Gordon, Michael J. Aziz","doi":"10.1038/s44286-024-00153-y","DOIUrl":"10.1038/s44286-024-00153-y","url":null,"abstract":"Here we elucidate the intricate interplay between the nucleophilicity swing and pH swing mechanisms in aqueous quinone-mediated carbon capture systems, showcasing the critical role of understanding this interplay in the material discovery cycle. This insight prompts the development of two in situ techniques. The first technique employs in situ reference electrodes and capitalizes on discernible voltage signature differences between quinones and quinone–CO2 adducts, allowing for the quantification of the isolated contributions of the two mechanisms. The second method is developed based on our finding that the adduct form of the quinone exhibits a fluorescence emission from an incident light at wavelengths distinct from the fluorescence of the reduced form. Thus, we introduce a noninvasive, in situ approach using fluorescence microscopy, providing the capability to distinguish species with subsecond time resolution at single-digit micrometer resolution. This technique holds promise for studying quinone-based systems for carbon capture and beyond. In an aqueous quinone-mediated system, both pH swing and nucleophilicity swing mechanisms contribute to CO2 capture, but traditional measurement methods report only the combined contributions, without quantifying their relative contributions. Here the authors introduce thermodynamic and kinetic analyses coupled with two in situ experimental techniques to quantify the contributions of these mechanisms.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 12","pages":"774-786"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Illuminating quinone-mediated CO2 capture and release","authors":"Shijie Liu, David Sinton","doi":"10.1038/s44286-024-00145-y","DOIUrl":"10.1038/s44286-024-00145-y","url":null,"abstract":"Electrochemical engineering offers a route to renewably powered CO2 capture. Now, fluorescence spectroscopy diagnostics provides a means to probe the fundamental mechanisms within these otherwise opaque systems.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 12","pages":"726-727"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Freezing droplet ejection by spring-like elastic pillars","authors":"Huanhuan Zhang, Wei Zhang, Yuankai Jin, Chenyang Wu, Zhenyu Xu, Siyan Yang, Shouwei Gao, Fayu Liu, Wanghuai Xu, Steven Wang, Haimin Yao, Zuankai Wang","doi":"10.1038/s44286-024-00150-1","DOIUrl":"10.1038/s44286-024-00150-1","url":null,"abstract":"Preventing water droplet accretion on surfaces is fundamentally interesting and practically important. Water droplets at room temperature can spontaneously detach from surfaces through texture design or coalescence-induced surface-to-kinetic energy transformation. However, under freezing conditions, these strategies become ineffective owing to the stronger droplet–surface interaction and the lack of an energy transformation pathway. Leveraging water volume expansion during freezing, we report a structured elastic surface with spring-like pillars and wetting contrast that renders the spontaneous ejection of freezing water droplets, regardless of their impacting locations. The spring-like pillars can store the work done by the seconds-long volume expansion of freezing droplets as elastic energy and then rapidly release it as kinetic energy within milliseconds. The three-orders-of-magnitude reduction in timescales leads to sufficient kinetic energy to drive freezing droplet ejection. We develop a theoretical model to elucidate the factors determining the successful onset of this phenomenon. Our design is potentially scalable in manufacturing through a numbering-up strategy, opening up applications in deicing, soft robotics and power generation. Preventing freezing droplet accretion on surfaces is practically important, yet challenging. Leveraging the water volume expansion during the freezing process, a structured elastic surface with spring-like pillars and wetting contrast is reported, which renders the spontaneous ejection of freezing water droplets, regardless of their impacting locations.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 12","pages":"765-773"},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linzixuan Zhang, Ruiqing Xiao, Tianyi Jin, Xinyan Pan, Katharina A. Fransen, Shahad K. Alsaiari, Alicia Lau, Ruizhe He, Jooli Han, Benjamin J. Pedretti, Jing Ying Yeo, Xin Yang, Bradley D. Olsen, Alfredo Alexander-Katz, Zachary P. Smith, Robert Langer, Ana Jaklenec
{"title":"Degradable poly(β-amino ester) microparticles for cleansing products and food fortification","authors":"Linzixuan Zhang, Ruiqing Xiao, Tianyi Jin, Xinyan Pan, Katharina A. Fransen, Shahad K. Alsaiari, Alicia Lau, Ruizhe He, Jooli Han, Benjamin J. Pedretti, Jing Ying Yeo, Xin Yang, Bradley D. Olsen, Alfredo Alexander-Katz, Zachary P. Smith, Robert Langer, Ana Jaklenec","doi":"10.1038/s44286-024-00151-0","DOIUrl":"10.1038/s44286-024-00151-0","url":null,"abstract":"Microplastic pollution is a pressing global crisis caused by the extensive use of nondegradable microplastic materials in daily activities. One effective approach to mitigate this issue is to replace nondegradable plastics with degradable materials that have properties amendable for targeted applications. Here we present the development of a degradable microparticle (MP) platform based on a poly(β-amino ester) (PAE) that degrades into sugar and amino acid derivatives. This PAE MP platform showed functional replacement of nondegradable microplastics used in cleansing products and food fortification. In cleansing products, PAE MPs effectively enhanced the cleansing efficiency of a representative rinse-off product and showed effective removal of potentially toxic elements, as an alternative of traditional nondegradable microbeads. In food fortification, PAE MPs provided robust protection for multiple essential vitamins and minerals against extensive cooking and storage conditions with rapid nutrient release in a simulated human digestion system. Collectively, these PAE MPs present a potential platform to replace microplastic usage on a global scale in many applications. This study reports the preparation of degradable poly(β-amino ester) microparticles as a promising replacement for nondegradable microplastics in cleansing products and food fortification, demonstrating effective cleansing, toxic element removal and robust nutrient protection with efficient release.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"2 1","pages":"77-89"},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A bacterial platform for producing aromatic esters from glycerol","authors":"Liangyu Lu, Xiaolei Wang, Tong Wang, Xiaolin Shen, Xinxiao Sun, Pingfang Tian, Yajun Yan, Jens Nielsen, Jia Wang, Qipeng Yuan","doi":"10.1038/s44286-024-00148-9","DOIUrl":"10.1038/s44286-024-00148-9","url":null,"abstract":"Aromatic esters possess flavor and fragrance qualities that are widely used in the food, pharmaceutical and cosmetic industries. However, microbial production of these compounds is hampered by a limited understanding of the natural biosynthetic pathway and the relatively low titer and yield. This study establishes a microbial platform for the efficient production of various aromatic esters. A systematic engineering strategy was developed, involving reshaping the substrate access tunnel to enhance enzyme substrate specificity, shifting acetyl coenzyme A metabolic pathways to improve cofactor supply and engineering a dynamic regulation system to redistribute the carbon flux from cell growth toward product synthesis. The implementation of these approaches led to the production of 10.4 g l–1 benzyl benzoate, representing a 4,700-fold increase in titer compared with the initial strain. This work showcases a bacterial platform for the efficient production of aromatic esters and offers insights into overcoming challenges in microbial cell factory construction. Biosynthesis of aromatic esters is challenged by unclear natural pathways and low efficiency. This study presents a bacterial platform for efficient production, using systematic engineering strategies including enzyme identification, reshaping enzyme tunnels and automating cellular resource allocation to enhance output.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 12","pages":"751-764"},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Streamlined aromatic ester process via tunnel engineering","authors":"Suk Min Kim, Yong Hwan Kim","doi":"10.1038/s44286-024-00149-8","DOIUrl":"10.1038/s44286-024-00149-8","url":null,"abstract":"The efficient production of high-value aromatic esters in microbial cell factories hinges on optimizing pathway specificity and resource allocation. Now, a study shows that employing both substrate tunnel engineering for enzyme specificity and dynamic metabolic regulation for resource allocation in Escherichia coli enables high-yield production of benzyl benzoate and other aromatic esters.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 12","pages":"728-730"},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adding big data into the equation","authors":"Joseph Sang-Il Kwon","doi":"10.1038/s44286-024-00142-1","DOIUrl":"10.1038/s44286-024-00142-1","url":null,"abstract":"Joseph Sang-Il Kwon explores how integrating big data with physics-based models can enhance accuracy and insights, particularly in drug discovery and solving high-dimensional problems.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 11","pages":"724-724"},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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