Nature Biomedical Engineering最新文献

Targeting vaccines to dendritic cells by mimicking the processing and presentation of antigens in xenotransplant rejection

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-13 DOI: 10.1038/s41551-025-01343-6

Jinjin Wang, Yuxuan Zhang, Yaru Jia, Haonan Xing, Fengfei Xu, Bozhang Xia, Wenjia Lai, Yuan Yuan, Xianlei Li, Shaobo Shan, Junge Chen, Weisheng Guo, Jinchao Zhang, Aiping Zheng, Jinghong Li, Ningqiang Gong, Xing-Jie Liang

{"title":"Targeting vaccines to dendritic cells by mimicking the processing and presentation of antigens in xenotransplant rejection","authors":"Jinjin Wang, Yuxuan Zhang, Yaru Jia, Haonan Xing, Fengfei Xu, Bozhang Xia, Wenjia Lai, Yuan Yuan, Xianlei Li, Shaobo Shan, Junge Chen, Weisheng Guo, Jinchao Zhang, Aiping Zheng, Jinghong Li, Ningqiang Gong, Xing-Jie Liang","doi":"10.1038/s41551-025-01343-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01343-6","url":null,"abstract":"Targeting the delivery of vaccines to dendritic cells (DCs) is challenging. Here we show that, by mimicking the fast and strong antigen processing and presentation that occurs during the rejection of xenotransplanted tissue, xenogeneic cell membrane-derived vesicles exposing tissue-specific antibodies can be leveraged to deliver peptide antigens and mRNA-encoded antigens to DCs. In mice with murine melanoma and murine thymoma, xenogeneic vesicles encapsulating a tumour-derived antigenic peptide or coated on lipid nanoparticles encapsulating an mRNA coding for a tumour antigen elicited potent tumour-specific T-cell responses that inhibited tumour growth. Mice immunized with xenogeneic vesicle-coated lipid nanoparticles encapsulating an mRNA encoding for the spike protein of severe acute respiratory syndrome coronavirus 2 elicited titres of anti-spike receptor-binding domain immunoglobulin G and of neutralizing antibodies that were approximately 32-fold and 6-fold, respectively, those elicited by a commercialized mRNA–lipid nanoparticle vaccine. The advantages of mimicking the biological recognition between immunoglobulin G on xenogeneic vesicles and fragment crystallizable receptors on DCs may justify the assessment of the safety risks of using animal-derived biological products in humans.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"29 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-12 DOI: 10.1038/s41551-025-01349-0

Alexandros P. Drainas, David R. McIlwain, Alec Dallas, Theresa Chu, Antonio Delgado-González, Maya Baron, Maria Angulo-Ibáñez, Angelica Trejo, Yunhao Bai, John W. Hickey, Guolan Lu, Scott Lu, Jesus Pineda-Ramirez, Khamal Anglin, Eugene T. Richardson, John C. Prostko, Edwin Frias, Venice Servellita, Noah Brazer, Charles Y. Chiu, Michael J. Peluso, Jeffrey N. Martin, Oliver F. Wirz, Tho D. Pham, Scott D. Boyd, J. Daniel Kelly, Julien Sage, Garry P. Nolan, Xavier Rovira-Clavé

{"title":"High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads","authors":"Alexandros P. Drainas, David R. McIlwain, Alec Dallas, Theresa Chu, Antonio Delgado-González, Maya Baron, Maria Angulo-Ibáñez, Angelica Trejo, Yunhao Bai, John W. Hickey, Guolan Lu, Scott Lu, Jesus Pineda-Ramirez, Khamal Anglin, Eugene T. Richardson, John C. Prostko, Edwin Frias, Venice Servellita, Noah Brazer, Charles Y. Chiu, Michael J. Peluso, Jeffrey N. Martin, Oliver F. Wirz, Tho D. Pham, Scott D. Boyd, J. Daniel Kelly, Julien Sage, Garry P. Nolan, Xavier Rovira-Clavé","doi":"10.1038/s41551-025-01349-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01349-0","url":null,"abstract":"In serology, each sample is typically tested individually, one antigen at a time. This is costly and time consuming. Serology techniques should ideally allow recurrent measurements in parallel in small sample volumes and be inexpensive and fast. Here we show that mass cytometry can be used to scale up multiplexed serology testing by leveraging polystyrene beads uniformly loaded with combinations of stable isotopes. We generated 18,480 unique isotopically barcoded beads to simultaneously detect, in a single tube with 924 serum samples, the levels of immunoglobulins G and M against 19 proteins from SARS-CoV-2 (a total of 36,960 tests in 400 nl of sample volume and 30 μl of reaction volume). As a rapid, high-throughput and cost-effective technique, serology by mass cytometry may contribute to the effective management of public health emergencies originating from infectious diseases.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"22 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-12 DOI: 10.1038/s41551-024-01318-z

Mattia Ballerini, Serena Galiè, Punit Tyagi, Carlotta Catozzi, Hariam Raji, Amir Nabinejad, Angeli D. G. Macandog, Alessandro Cordiale, Bianca Ionela Slivinschi, Karol K. Kugiejko, Martina Freisa, Paola Occhetta, Jennifer A. Wargo, Pier F. Ferrucci, Emilia Cocorocchio, Nicola Segata, Andrea Vignati, Andrey Morgun, Michela Deleidi, Teresa Manzo, Marco Rasponi, Luigi Nezi

{"title":"A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma","authors":"Mattia Ballerini, Serena Galiè, Punit Tyagi, Carlotta Catozzi, Hariam Raji, Amir Nabinejad, Angeli D. G. Macandog, Alessandro Cordiale, Bianca Ionela Slivinschi, Karol K. Kugiejko, Martina Freisa, Paola Occhetta, Jennifer A. Wargo, Pier F. Ferrucci, Emilia Cocorocchio, Nicola Segata, Andrea Vignati, Andrey Morgun, Michela Deleidi, Teresa Manzo, Marco Rasponi, Luigi Nezi","doi":"10.1038/s41551-024-01318-z","DOIUrl":"https://doi.org/10.1038/s41551-024-01318-z","url":null,"abstract":"Patient responses to immune checkpoint inhibitors can be influenced by the gastrointestinal microbiome. Mouse models can be used to study microbiome–host crosstalk, yet their utility is constrained by substantial anatomical, functional, immunological and microbial differences between mice and humans. Here we show that a gut-on-a-chip system mimicking the architecture and functionality of the human intestine by including faecal microbiome and peristaltic-like movements recapitulates microbiome–host interactions and predicts responses to immune checkpoint inhibitors in patients with melanoma. The system is composed of a vascular channel seeded with human microvascular endothelial cells and an intestinal channel with intestinal organoids derived from human induced pluripotent stem cells, with the two channels separated by a collagen matrix. By incorporating faecal samples from patients with melanoma into the intestinal channel and by performing multiomic analyses, we uncovered epithelium-specific biomarkers and microbial factors that correlate with clinical outcomes in patients with melanoma and that the microbiome of non-responders has a reduced ability to buffer cellular stress and self-renew. The gut-on-a-chip model may help identify prognostic biomarkers and therapeutic targets.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"30 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synaptic connectivity mapping among thousands of neurons via parallelized intracellular recording with a microhole electrode array

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-11 DOI: 10.1038/s41551-025-01352-5

Jun Wang, Woo-Bin Jung, Rona S. Gertner, Hongkun Park, Donhee Ham

{"title":"Synaptic connectivity mapping among thousands of neurons via parallelized intracellular recording with a microhole electrode array","authors":"Jun Wang, Woo-Bin Jung, Rona S. Gertner, Hongkun Park, Donhee Ham","doi":"10.1038/s41551-025-01352-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01352-5","url":null,"abstract":"The massive parallelization of neuronal intracellular recording, which enables the measurement of synaptic signals across a neuronal network, and thus the mapping and characterization of synaptic connections, is an open challenge, with the state of the art being limited to the mapping of about 300 synaptic connections. Here we report a 4,096 platinum/platinum-black microhole electrode array fabricated on a complementary metal-oxide semiconductor chip for parallel intracellular recording and thus for synaptic-connectivity mapping. The microhole–neuron interface, together with current-clamp electronics in the underlying semiconductor chip, allowed a 90% average intracellular coupling rate in rat neuronal cultures, generating network-wide intracellular-recording data with abundant synaptic signals. From these data, we extracted more than 70,000 plausible synaptic connections among more than 2,000 neurons and catalogued them into electrical synaptic connections and into inhibitory, weak/uneventful excitatory and strong/eventful excitatory chemical synaptic connections, with an estimated overall error rate of about 5%. This scale of synaptic-connectivity mapping and the ability to characterize synaptic connections is a step towards the functional connectivity mapping of large-scale neuronal networks.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"21 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Small circular RNAs as vaccines for cancer immunotherapy

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-07 DOI: 10.1038/s41551-025-01344-5

Yu Zhang, Xiang Liu, Tingting Shen, Qiyan Wang, Shurong Zhou, Suling Yang, Shimiao Liao, Ting Su, Lei Mei, Bei Zhang, Khoa Huynh, Linying Xie, Youzhong Guo, Chunqing Guo, Katarzyna M. Tyc, Xufeng Qu, Xiang-Yang Wang, Jinze Liu, Guizhi Zhu

{"title":"Small circular RNAs as vaccines for cancer immunotherapy","authors":"Yu Zhang, Xiang Liu, Tingting Shen, Qiyan Wang, Shurong Zhou, Suling Yang, Shimiao Liao, Ting Su, Lei Mei, Bei Zhang, Khoa Huynh, Linying Xie, Youzhong Guo, Chunqing Guo, Katarzyna M. Tyc, Xufeng Qu, Xiang-Yang Wang, Jinze Liu, Guizhi Zhu","doi":"10.1038/s41551-025-01344-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01344-5","url":null,"abstract":"Messenger RNA vaccines have shown strong prophylactic efficacy against viral infections. Here we show that antigen-encoding small circular RNAs (circRNAs) loaded in lipid nanoparticles elicit potent and durable T cell responses for robust tumour immunotherapy after subcutaneous injection in mice, particularly when combined with immune checkpoint inhibition. The small circRNA vaccines are highly stable and show low levels of activation of protein kinase R as well as low cytotoxicity, enabling long-lasting antigen translation (longer than 1 week in cells). Relative to large protein-encoding unmodified or modified mRNAs and circRNAs, small circRNA vaccines elicited up to 10-fold antigen-specific T cells in mice and accounted for 30–75% of the total peripheral CD8+ T cells over 6 months. Small circRNA vaccines encoding tumour-associated antigens, neoantigens and oncoviral or viral antigens elicited substantial CD8+ and CD4+ T cell responses in young adult mice and in immunosenescent aged mice. Combined with immune checkpoint inhibition, monovalent and multivalent circRNA vaccines reduced tumour-induced immunosuppression and inhibited poorly immunogenic mouse tumours, including melanoma resistant to immune checkpoint blockade.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"13 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTENmRNA

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-05 DOI: 10.1038/s41551-025-01358-z

Mohammad Ariful Islam, Yingjie Xu, Wei Tao, Jessalyn M. Ubellacker, Michael Lim, Daniel Aum, Gha Young Lee, Kun Zhou, Harshal Zope, Mikyung Yu, Wuji Cao, James Trevor Oswald, Meshkat Dinarvand, Morteza Mahmoudi, Robert Langer, Philip W. Kantoff, Omid C. Farokhzad, Bruce R. Zetter, Jinjun Shi

引用次数: 0

Author Correction: A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-05 DOI: 10.1038/s41551-025-01359-y

Christopher L. Yankaskas, Keyata N. Thompson, Colin D. Paul, Michele I. Vitolo, Panagiotis Mistriotis, Ankit Mahendra, Vivek K. Bajpai, Daniel J. Shea, Kristen M. Manto, Andreas C. Chai, Navin Varadarajan, Aikaterini Kontrogianni-Konstantopoulos, Stuart S. Martin, Konstantinos Konstantopoulos

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Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-05 DOI: 10.1038/s41551-024-01341-0

Alan Rosales, Leo O. Blondel, Joshua Hull, Qimeng Gao, Nihal Aykun, Jennifer L. Peek, Alejandra Vargas, Sophia Fergione, Mingqing Song, Matthew H. Wilson, Andrew S. Barbas, Aravind Asokan

{"title":"Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries","authors":"Alan Rosales, Leo O. Blondel, Joshua Hull, Qimeng Gao, Nihal Aykun, Jennifer L. Peek, Alejandra Vargas, Sophia Fergione, Mingqing Song, Matthew H. Wilson, Andrew S. Barbas, Aravind Asokan","doi":"10.1038/s41551-024-01341-0","DOIUrl":"https://doi.org/10.1038/s41551-024-01341-0","url":null,"abstract":"The difficulty of delivering genes to the kidney has limited the translation of genetic medicines, particularly for the more than 10% of the global population with chronic kidney disease. Here we show that new variants of adeno-associated viruses (AAVs) displaying robust and widespread transduction in the kidneys of mice, pigs and non-human-primates can be obtained by evolving capsid libraries via cross-species cycling in different kidney models. Specifically, the new variants, AAV.k13 and AAV.k20, were enriched from the libraries following sequential intravenous cycling through mouse and pig kidneys, ex vivo cycling in human organoid cultures, and ex vivo machine perfusion in isolated kidneys from rhesus macaques. The two variants transduced murine kidneys following intravenous administration, with selective tropism for proximal tubules, and led to markedly higher transgene expression than parental AAV9 vectors in proximal tubule epithelial cells within human organoid cultures and in autotransplanted pig kidneys. Following ureteral delivery, AAV.k20 efficiently transduced kidneys in pigs and macaques. The AAV.k13 and AAV.k20 variants are promising vectors for therapeutic gene-transfer applications in kidney diseases and transplantation.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"123 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Enhanced control of a brain–computer interface by tetraplegic participants via neural-network-mediated feature extraction

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-01-29 DOI: 10.1038/s41551-025-01355-2

Benyamin Haghi, Tyson Aflalo, Spencer Kellis, Charles Guan, Jorge A. Gamez de Leon, Albert Yan Huang, Nader Pouratian, Richard A. Andersen, Azita Emami

引用次数: 0

Urinary bioorthogonal reporters for the monitoring of the efficacy of chemotherapy for lung cancer and of associated kidney injury

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-01-29 DOI: 10.1038/s41551-024-01340-1

Penghui Cheng, Ziling Zeng, Jing Liu, Si Si Liew, Yuxuan Hu, Mengke Xu, Kanyi Pu

{"title":"Urinary bioorthogonal reporters for the monitoring of the efficacy of chemotherapy for lung cancer and of associated kidney injury","authors":"Penghui Cheng, Ziling Zeng, Jing Liu, Si Si Liew, Yuxuan Hu, Mengke Xu, Kanyi Pu","doi":"10.1038/s41551-024-01340-1","DOIUrl":"https://doi.org/10.1038/s41551-024-01340-1","url":null,"abstract":"The utility of urinary tests for the monitoring of the treatment efficacy and adverse events of anticancer therapies is constrained by the low concentration of relevant urinary biomarkers. Here we report, using mice with lung cancer and treated with chemotherapy, of a urinary fluorescence test for the concurrent monitoring of the levels of a tumour biomarker (cathepsin B) and of a biomarker of chemotherapy-induced kidney injury (N-acetyl-β-d-glucosaminidase). The test involves two intratracheally administered urinary reporters leveraging caged bioorthogonal click handles for the biomarker-dependent activation of ‘clickability’ and renal clearance, and the bioorthogonal click reaction of each renally cleared reporter with paired fluorescence indicators in the collected urine. In mouse models of chemotherapy-treated orthotopic lung cancer and of cisplatin-induced kidney injury, lower urinary fluorescence signals (which can be measured by a smartphone camera) for tumour and kidney injury levels positively correlated with animal weight gain and survival time. Biomarker-activated bioorthogonal click reactivity and renal clearance combined with bioorthogonally triggered fluorescence in vitro may enable specific, sensitive and rapid urinary assays for the monitoring of other physiopathological processes.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"40 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0