{"title":"Engineering circular RNA medicines","authors":"Xiaofei Cao, Zhengyi Cai, Jinyang Zhang, Fangqing Zhao","doi":"10.1038/s44222-024-00259-1","DOIUrl":"10.1038/s44222-024-00259-1","url":null,"abstract":"Circular RNAs (circRNAs) are a group of RNA molecules prevalent across various organisms and tissues and characterized by a covalent loop structure. Their unique structure, lacking 5′ and 3′ ends, confers resistance to exonucleases, thereby enhancing their stability compared to linear RNAs. Since the early 2010s, the versatility of circRNAs have been highlighted in applications such as RNA aptamers, guide RNAs and, more recently, SARS-CoV-2 vaccines. Recent advances in rational design, as well as in vitro and in vivo synthesis techniques, underscore the potential for large-scale engineering and production of circRNAs, positioning them as promising candidates for stable and efficient RNA-based therapeutics with minimal immunogenicity. This Review summarizes the guiding principles behind circRNA engineering and development, with a focus on key design elements. We also provide an overview of circRNA advances in disease prevention and treatment. By emphasizing existing limitations and outlining future milestones, this Review offers a translational outlook on circRNAs as an emerging field in biomedicine. Compared to linear mRNA, circular RNAs offer greater stability during storage and delivery, along with more sustained effects due to their circular structure. This Review provides an overview of circRNA-based therapeutics, highlighting key engineering principles, associated challenges and strategies to address such challenges.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 4","pages":"270-287"},"PeriodicalIF":37.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122666","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}
Mauro Manno, Antonella Bongiovanni, Leonid Margolis, Paolo Bergese, Paolo Arosio
{"title":"The physico-chemical landscape of extracellular vesicles","authors":"Mauro Manno, Antonella Bongiovanni, Leonid Margolis, Paolo Bergese, Paolo Arosio","doi":"10.1038/s44222-024-00255-5","DOIUrl":"10.1038/s44222-024-00255-5","url":null,"abstract":"Extracellular vesicles are defined as nanosized to microsized particles, delimited by a lipid bilayer membrane, that seem to be released by all cell types and that can transport bioactive molecules between cells, tissues, organs and organisms. Therefore, extracellular vesicles are being explored as biomaterials, drug delivery nanocarriers, therapeutics and multiplexed biomarkers. However, the isolation, characterization and large-scale manufacturing of extracellular vesicles remains challenging. In this Review, we delineate the landscape of the physico-chemical properties of extracellular vesicles, originating from their composition and conformational ensemble, and outline how this landscape is defined by the heterogeneity of their size, composition, membrane structure, surface interactions, cargo and co-isolates. We explore the implications of this heterogeneity on the definition of the purity, identity and function of extracellular vesicles. The comparison of this landscape with the landscape of antibody therapeutics and viral vectors can identify lessons to be learned from the bioprocessing of these products, and the distinct challenges associated with the manufacturing and isolation of extracellular vesicles from biofluids, which will require new concepts and technologies. We highlight the importance of a thorough understanding of the physico-chemical properties of extracellular vesicles for their clinical translation. This includes the development of bioprocessing approaches, assignment of product quality attributes, consistency of extracellular vesicle products and manufacturing at scale. Extracellular vesicles are being explored for various biomedical applications, but face challenges with regard to isolation, characterization and manufacturing. This Review delineates the physico-chemical landscape of extracellular vesicles to identify the distinct challenges associated with the manufacturing and isolation of extracellular vesicles from biofluids and suggests opportunities to address them.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 1","pages":"68-82"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976678","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":"How to write an excellent Review article","authors":"","doi":"10.1038/s44222-024-00256-4","DOIUrl":"10.1038/s44222-024-00256-4","url":null,"abstract":"Review articles are our bread and butter. Here, we would like to offer some insights on how to craft a comprehensive and authoritative assessment of a field.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 11","pages":"907-907"},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44222-024-00256-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599014","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":"Imaging-guided precision hyperthermia with magnetic nanoparticles","authors":"Ali Shakeri-Zadeh, Jeff W. M. Bulte","doi":"10.1038/s44222-024-00257-3","DOIUrl":"10.1038/s44222-024-00257-3","url":null,"abstract":"Magnetic nanoparticles, including those formed of superparamagnetic iron oxides (SPIOs), are employed in various magnetic imaging and therapeutic techniques. In vivo imaging techniques based on the detection of magnetic nanoparticles inside the body include magnetic resonance imaging (MRI), magnetic particle imaging (MPI), magneto-motive ultrasonography (MMUS) and magneto-photoacoustic imaging (MPAI). Preclinical data indicate that the conditions required to heat up magnetic nanoparticles, including energy considerations, particle modifications, localization and exposure time, can be dynamically modulated during a single treatment procedure by monitoring imaging data acquired from the same magnetic nanoparticles. This Review explores the potential use of magnetic-nanoparticle-mediated imaging techniques combined with magnetic fluid hyperthermia (MFH) to selectively and precisely heat tumour locations while avoiding damage to surrounding healthy tissue. Imaging-guided MFH could provide individualized treatment plans based on information about the biodistribution of magnetic nanoparticles within the tumour and adjacent organs, as well as the volumetric distribution of the thermal dose. Requirements for the clinical translation of MFH-enabled magnetic imaging techniques are also discussed — the development of magnetic nanoparticle formulations with a favourable biosafety profile, optimal magnetic heating properties and maximal magnetic imaging signals; and the integration of magnetic imaging and heating hardware into a single platform. This Review details the use of multifunctional magnetic nanoparticles in advanced magnetic imaging modalities and therapeutic hyperthermia. The potential of magnetic nanoparticles for imaging-guided precision heating of tumours and the need for integrated magnetic imaging and heating platforms are highlighted.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 3","pages":"245-260"},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633146","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":"Cryopreservation of in vitro human tissue models","authors":"Yaqi Sheng, Yan Yan Shery Huang","doi":"10.1038/s44222-024-00261-7","DOIUrl":"10.1038/s44222-024-00261-7","url":null,"abstract":"The widespread use and translation of engineered in vitro tissues, such as organoids, organ-on-chip devices and microphysiological models, will require designs that can be preserved by cryopreservation. Here, we outline the factors that affect their cryopreservation, highlighting the challenges that remain to be addressed.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 1","pages":"4-6"},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976686","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}
Xin Guan (, ), Guohui Ji (, ), Guocheng Du (, ), Jian Chen (, ), Jingwen Zhou (, )
{"title":"Microbial cell factories for cost-effective and high-quality cultured meat","authors":"Xin Guan \u0000 (, ), Guohui Ji \u0000 (, ), Guocheng Du \u0000 (, ), Jian Chen \u0000 (, ), Jingwen Zhou \u0000 (, )","doi":"10.1038/s44222-024-00258-2","DOIUrl":"10.1038/s44222-024-00258-2","url":null,"abstract":"Commercializing cultured meat requires cost reduction and quality improvement. Microbial cell factories can produce cost-effective and high-quality raw materials for cultured meat production.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 1","pages":"7-8"},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976687","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}
Abhishek P. Dhand, Matthew D. Davidson, Jason A. Burdick
{"title":"Lithography-based 3D printing of hydrogels","authors":"Abhishek P. Dhand, Matthew D. Davidson, Jason A. Burdick","doi":"10.1038/s44222-024-00251-9","DOIUrl":"10.1038/s44222-024-00251-9","url":null,"abstract":"Additive manufacturing is an engineering tool that enables the creation of complex structures for biomedical use, such as 3D scaffolds for tissue engineering and regenerative medicine, as well as in vitro disease models for drug testing. In particular, lithography-based techniques such as digital light processing and volumetric additive manufacturing have enabled advances in the 3D processing of photoreactive resins into structured hydrogels. In this Review, we introduce light-based lithographic 3D printing methods to process hydrogels and provide a guide to lithography-based printing, from bioresin selection to the optimization of print parameters. Moreover, we highlight examples of in vitro and in vivo biomedical applications of hydrogels, for which lithography-based approaches have been leveraged, and discuss efforts to process hydrogels into heterogeneous structures with multi-scale organization. Finally, we provide a perspective on the challenges and opportunities in this field. Lithography-based 3D printing has emerged as a valuable tool with which to develop hydrogels for biomedical applications. This Review discusses lithography-based 3D printing techniques, offers guidance for resin formulation and provides a step-by-step manual for printing hydrogels intended for clinical applications.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 2","pages":"108-125"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44222-024-00251-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397412","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}
Bin Long, Fuzhong Zhang, Susie Y. Dai, Marcus Foston, Yinjie J. Tang, Joshua S. Yuan
{"title":"Engineering strategies to optimize lignocellulosic biorefineries","authors":"Bin Long, Fuzhong Zhang, Susie Y. Dai, Marcus Foston, Yinjie J. Tang, Joshua S. Yuan","doi":"10.1038/s44222-024-00247-5","DOIUrl":"10.1038/s44222-024-00247-5","url":null,"abstract":"Lignocellulosic biorefineries may be applied to produce value-added products, such as chemicals, biofuels and bioplastics, from biomass, thereby reducing carbon emissions compared with fossil fuel-based products. However, efficient biomass valorization remains challenging owing to limitations in yields and economic viability. In this Review, we discuss engineering strategies to improve lignocellulosic biomass-based production, including approaches to optimize biomass deconstruction, substrate utilization, productivity, strain robustness and fermentation stability. We further highlight the importance of systems and synthetic biology tools, artificial intelligence, and automation in the design and scale-up of lignocellulosic biorefineries, emphasizing the integration of techno-economic analysis and life-cycle assessment. These tools may assist in investigating microbial metabolism, accelerating microbial metabolic engineering, enhancing substrate-to-product bioconversion, and optimizing the economics and environmental impact of biorefineries. Biomass, such as lignocellulose, can be processed into value-added products and energy, offering a promising solution for carbon-neutral chemical and fuel production. This Review discusses engineering strategies, including systems and synthetic biology approaches, to optimize lignocellulose biorefineries.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 3","pages":"230-244"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633141","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}
Joshua A. Homer, Robert M. Johnson, Rebecca A. Koelln, Adam D. Moorhouse, John E. Moses
{"title":"Strategic re-engineering of antibiotics","authors":"Joshua A. Homer, Robert M. Johnson, Rebecca A. Koelln, Adam D. Moorhouse, John E. Moses","doi":"10.1038/s44222-024-00250-w","DOIUrl":"10.1038/s44222-024-00250-w","url":null,"abstract":"Multidrug-resistant bacteria, especially those that defy even last-resort antibiotics, are causing a global health crisis fuelled by antibiotic overuse and misuse as well as the lack of development of new antibiotics. Multidrug-resistant bacteria compromise our ability to effectively treat infections, affecting medical procedures such as surgeries and cancer treatments while increasing illness duration, mortality rates and healthcare costs. In this Review, we discuss re-engineering approaches for existing antibiotics to address multidrug-resistant bacterial infections. We outline how antibiotic activity against drug-resistant bacteria can be increased through structural modifications and by engineering polyvalent drugs and combination therapies designed to overcome drug-resistance mechanisms. Finally, we examine the regulatory and translational challenges for antibiotic re-engineering, highlighting the need for antibiotic stewardship and global guidelines. The global rise of drug-resistant bacteria, including those resistant to last-resort antibiotics, poses an urgent health threat. This Review discusses antibiotic re-engineering strategies to increase the activity and improve the efficacy of existing antibiotics against multidrug-resistant infections.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 3","pages":"213-229"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633142","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":"Funding research on women’s health","authors":"","doi":"10.1038/s44222-024-00253-7","DOIUrl":"10.1038/s44222-024-00253-7","url":null,"abstract":"Women’s health research has long been underfunded, in part owing to stigmas associated with conditions that primarily affect women. Equitable health research funding requires transparency from funding agencies, investment in women-centred innovations, support for women in science and a cultural shift in how health issues are viewed.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 10","pages":"797-798"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44222-024-00253-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142415432","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}
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