Nature Biomedical Engineering最新文献_第10页

Safer and efficient base editing and prime editing via ribonucleoproteins delivered through optimized lipid-nanoparticle formulations 通过优化的脂质纳米颗粒配方输送核糖核蛋白，实现更安全高效的碱基编辑和基质编辑

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-28 DOI: 10.1038/s41551-024-01296-2

Rafał Hołubowicz, Samuel W. Du, Jiin Felgner, Roman Smidak, Elliot H. Choi, Grazyna Palczewska, Carolline Rodrigues Menezes, Zhiqian Dong, Fangyuan Gao, Omar Medani, Alexander L. Yan, Maria W. Hołubowicz, Paul Z. Chen, Marco Bassetto, Eleonora Risaliti, David Salom, J. Noah Workman, Philip D. Kiser, Andrzej T. Foik, David C. Lyon, Gregory A. Newby, David R. Liu, Philip L. Felgner, Krzysztof Palczewski

{"title":"Safer and efficient base editing and prime editing via ribonucleoproteins delivered through optimized lipid-nanoparticle formulations","authors":"Rafał Hołubowicz, Samuel W. Du, Jiin Felgner, Roman Smidak, Elliot H. Choi, Grazyna Palczewska, Carolline Rodrigues Menezes, Zhiqian Dong, Fangyuan Gao, Omar Medani, Alexander L. Yan, Maria W. Hołubowicz, Paul Z. Chen, Marco Bassetto, Eleonora Risaliti, David Salom, J. Noah Workman, Philip D. Kiser, Andrzej T. Foik, David C. Lyon, Gregory A. Newby, David R. Liu, Philip L. Felgner, Krzysztof Palczewski","doi":"10.1038/s41551-024-01296-2","DOIUrl":"10.1038/s41551-024-01296-2","url":null,"abstract":"Delivering ribonucleoproteins (RNPs) for in vivo genome editing is safer than using viruses encoding for Cas9 and its respective guide RNA. However, transient RNP activity does not typically lead to optimal editing outcomes. Here we show that the efficiency of delivering RNPs can be enhanced by cell-penetrating peptides (covalently fused to the protein or as excipients) and that lipid nanoparticles (LNPs) encapsulating RNPs can be optimized for enhanced RNP stability, delivery efficiency and editing potency. Specifically, after screening for suitable ionizable cationic lipids and by optimizing the concentration of the synthetic lipid DMG-PEG 2000, we show that the encapsulation, via microfluidic mixing, of adenine base editor and prime editor RNPs within LNPs using the ionizable lipid SM102 can result in in vivo editing-efficiency enhancements larger than 300-fold (with respect to the delivery of the naked RNP) without detectable off-target edits. We believe that chemically defined LNP formulations optimized for RNP-encapsulation stability and delivery efficiency will lead to safer genome editing. The safety and efficacy of ribonucleoproteins for genome editing can be enhanced by formulations of lipid nanoparticles optimized for enhanced stability, delivery efficiency and editing potency of the protein complexes.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 1","pages":"57-78"},"PeriodicalIF":26.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41551-024-01296-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antitumour vaccination via the targeted proteolysis of antigens isolated from tumour lysates 通过对从肿瘤裂解物中分离出来的抗原进行靶向蛋白水解来接种抗肿瘤疫苗

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-28 DOI: 10.1038/s41551-024-01285-5

Yu Zhao, Donghui Song, Zeyu Wang, Qingqing Huang, Fan Huang, Zhongfeng Ye, Douglas Wich, Mengting Chen, Jennifer Khirallah, Shuliang Gao, Yang Liu, Qiaobing Xu

{"title":"Antitumour vaccination via the targeted proteolysis of antigens isolated from tumour lysates","authors":"Yu Zhao, Donghui Song, Zeyu Wang, Qingqing Huang, Fan Huang, Zhongfeng Ye, Douglas Wich, Mengting Chen, Jennifer Khirallah, Shuliang Gao, Yang Liu, Qiaobing Xu","doi":"10.1038/s41551-024-01285-5","DOIUrl":"10.1038/s41551-024-01285-5","url":null,"abstract":"The activation of cytotoxic T cells against tumour cells typically requires the cross-presentation, by antigen-presenting cells (and via major histocompatibility complex class I molecules), of an epitope derived from a tumour antigen. A critical step in antigen processing is the proteolysis of tumour antigens mediated by the ubiquitin–proteasome pathway. Here we describe a tumour vaccine leveraging targeted antigen degradation to augment antigen processing and cross-presentation. Analogous to proteolysis-targeting chimaeras, the vaccine consists of lymph-node-targeting lipid nanoparticles encapsulated with tumour antigens pre-conjugated with ligands that can bind to E3 ubiquitin ligases. In mice with subcutaneous human melanoma or triple-negative breast cancer, or with orthotopic mouse Lewis lung carcinoma or clinically inoperable mouse ovarian cancer, subcutaneously delivered vaccines prepared using tumour lysate proteins elicited antigen-specific adaptive immunity and immunological memory, and inhibited tumour growth, metastasis and recurrence, particularly when combined with immune checkpoint inhibition. A tumour vaccine leveraging the targeted degradation of antigens isolated from tumour lysates augmented antigen processing and cross-presentation, and inhibited tumour growth, metastasis and recurrence in multiple mouse models of cancers.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 2","pages":"234-248"},"PeriodicalIF":26.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735668","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

Diagnosis of early-stage bladder cancer via unprocessed urine samples at the point of care 在医疗点通过未经处理的尿液样本诊断早期膀胱癌

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-28 DOI: 10.1038/s41551-024-01298-0

Changjoon Keum, Haejin Yeom, Tae Il Noh, Seung Yong Yi, Soyeong Jin, Chaekyu Kim, Ji Sung Shim, Sung Goo Yoon, Hojun Kim, Kwan Hyi Lee, Seok Ho Kang, Youngdo Jeong

{"title":"Diagnosis of early-stage bladder cancer via unprocessed urine samples at the point of care","authors":"Changjoon Keum, Haejin Yeom, Tae Il Noh, Seung Yong Yi, Soyeong Jin, Chaekyu Kim, Ji Sung Shim, Sung Goo Yoon, Hojun Kim, Kwan Hyi Lee, Seok Ho Kang, Youngdo Jeong","doi":"10.1038/s41551-024-01298-0","DOIUrl":"https://doi.org/10.1038/s41551-024-01298-0","url":null,"abstract":"Diagnostic kits for the optical detection of bladder cancer in urine can facilitate effective screening and surveillance. However, the heterogeneity of urine samples, owing to patients with bladder cancer often presenting with haematuria, interfere with the transduction of the optical signal. Here we describe the development and point-of-care performance of a device for the detection of bladder cancer that obviates the need for sample processing. The device leverages the enzymatic release of organogel particles carrying solvatochromic fluorophores in the presence of urinary hyaluronidases—a bladder cancer biomarker. Owing to buoyancy, the particles transfer from the urine sample into the organic phase, where the change in fluorescence can be measured via a smartphone without interference from blood proteins. In a double-blind study with 80 unprocessed urine samples from patients with bladder cancer (including samples with haematuria) or other genitourinary diseases and with 25 samples from healthy participants, our system distinguished the cancerous samples, including those with early-stage bladder cancer, with accuracies of about 90%. Obviating the need for sample pretreatment may facilitate the at-home detection of bladder cancer.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735592","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

Optimization of the activity and biodegradability of ionizable lipids for mRNA delivery via directed chemical evolution 通过定向化学进化优化可离子化脂质的活性和生物降解性，用于 mRNA 输送

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-22 DOI: 10.1038/s41551-024-01267-7

Xuexiang Han, Mohamad-Gabriel Alameh, Ying Xu, Rohan Palanki, Rakan El-Mayta, Garima Dwivedi, Kelsey L. Swingle, Junchao Xu, Ningqiang Gong, Lulu Xue, Qiangqiang Shi, Il-Chul Yoon, Claude C. Warzecha, James M. Wilson, Drew Weissman, Michael J. Mitchell

{"title":"Optimization of the activity and biodegradability of ionizable lipids for mRNA delivery via directed chemical evolution","authors":"Xuexiang Han, Mohamad-Gabriel Alameh, Ying Xu, Rohan Palanki, Rakan El-Mayta, Garima Dwivedi, Kelsey L. Swingle, Junchao Xu, Ningqiang Gong, Lulu Xue, Qiangqiang Shi, Il-Chul Yoon, Claude C. Warzecha, James M. Wilson, Drew Weissman, Michael J. Mitchell","doi":"10.1038/s41551-024-01267-7","DOIUrl":"10.1038/s41551-024-01267-7","url":null,"abstract":"Ionizable lipids largely determine the biocompatibility of lipid nanoparticles (LNPs) and the efficacy for mRNA delivery. Rational design and combinatorial synthesis have led to the development of potent and biodegradable ionizable lipids, yet methodologies for the stepwise optimization of ionizable lipid structure are lacking. Here we show that iterative chemical derivatization and combinatorial chemistry, and in particular the amine–aldehyde–alkyne coupling reaction, can be leveraged to iteratively accelerate the structural optimization of propargylamine-based ionizable lipids (named A3-lipids) to improve their delivery activity and biodegradability. Through five cycles of such directed chemical evolution, we identified dozens of biodegradable and asymmetric A3-lipids with delivery activity comparable to or better than a benchmark ionizable lipid. We then derived structure−activity relationships for the headgroup, ester linkage and tail. Compared with standard ionizable lipids, the lead A3-lipid improved the hepatic delivery of an mRNA-based genome editor and the intramuscular delivery of an mRNA vaccine against SARS-CoV-2. Structural criteria for ionizable lipids discovered via directed chemical evolution may accelerate the development of LNPs for mRNA delivery. Directed chemical evolution can iteratively accelerate the structural optimization of ionizable lipids to improve their delivery activity and biodegradability for applications in lipid nanoparticle-mediated mRNA delivery.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 11","pages":"1412-1424"},"PeriodicalIF":26.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684272","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

Offbeat drug-delivery tactics 非传统的给药策略

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-22 DOI: 10.1038/s41551-024-01317-0

引用次数: 0

Solvent-mediated analgesia via the suppression of water permeation through TRPV1 ion channels 通过抑制 TRPV1 离子通道的水渗透实现溶剂介导的镇痛作用

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-21 DOI: 10.1038/s41551-024-01288-2

Yuxia Liu, Yuanyuan He, Jiahuan Tong, Shengyang Guo, Xinyu Zhang, Zichao Luo, Linlin Sun, Chao Chang, Bilin Zhuang, Xiaogang Liu

{"title":"Solvent-mediated analgesia via the suppression of water permeation through TRPV1 ion channels","authors":"Yuxia Liu, Yuanyuan He, Jiahuan Tong, Shengyang Guo, Xinyu Zhang, Zichao Luo, Linlin Sun, Chao Chang, Bilin Zhuang, Xiaogang Liu","doi":"10.1038/s41551-024-01288-2","DOIUrl":"https://doi.org/10.1038/s41551-024-01288-2","url":null,"abstract":"Activation of the ion channel transient receptor potential vanilloid 1 (TRPV1), which is integral to pain perception, leads to an expansion of channel width, facilitating the passage of cations and large organic molecules. However, the permeability of TRPV1 channels to water remains uncertain, owing to a lack of suitable tools to study water dynamics. Here, using upconversion nanophosphors to discriminate between H2O and D2O, by monitoring water permeability across activated TRPV1 at the single-cell and single-molecule levels, and by combining single-channel current measurements with molecular dynamics simulations, we show that water molecules flow through TRPV1 and reveal a direct connection between water migration, cation flow and TRPV1 functionality. We also show in mouse models of acute or chronic inflammatory pain that the administration of deuterated water suppresses TRPV1 activity, interrupts the transmission of pain signals and mitigates pain without impacting other neurological responses. Solvent-mediated analgesia may inspire alternative options for pain management.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"11 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678280","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

Clinical validation of a wearable ultrasound sensor of blood pressure 可穿戴式超声波血压传感器的临床验证

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-20 DOI: 10.1038/s41551-024-01279-3

Sai Zhou, Geonho Park, Katherine Longardner, Muyang Lin, Baiyan Qi, Xinyi Yang, Xiaoxiang Gao, Hao Huang, Xiangjun Chen, Yizhou Bian, Hongjie Hu, Ray S. Wu, Wentong Yue, Mohan Li, Chengchangfeng Lu, Ruotao Wang, Siyu Qin, Esra Tasali, Theodore Karrison, Isac Thomas, Benjamin Smarr, Erik B. Kistler, Belal Al Khiami, Irene Litvan, Sheng Xu

{"title":"Clinical validation of a wearable ultrasound sensor of blood pressure","authors":"Sai Zhou, Geonho Park, Katherine Longardner, Muyang Lin, Baiyan Qi, Xinyi Yang, Xiaoxiang Gao, Hao Huang, Xiangjun Chen, Yizhou Bian, Hongjie Hu, Ray S. Wu, Wentong Yue, Mohan Li, Chengchangfeng Lu, Ruotao Wang, Siyu Qin, Esra Tasali, Theodore Karrison, Isac Thomas, Benjamin Smarr, Erik B. Kistler, Belal Al Khiami, Irene Litvan, Sheng Xu","doi":"10.1038/s41551-024-01279-3","DOIUrl":"https://doi.org/10.1038/s41551-024-01279-3","url":null,"abstract":"Options for the continuous and non-invasive monitoring of blood pressure are limited. Cuff-based sphygmomanometers are widely available, yet provide only discrete measurements. The clinical gold-standard approach for the continuous monitoring of blood pressure requires an arterial line, which is too invasive for routine use. Wearable ultrasound for the continuous and non-invasive monitoring of blood pressure promises to elevate the quality of patient care, yet the isolated sonographic windows in the most advanced prototypes can lead to inaccurate or error-prone measurements, and the safety and performance of these devices have not been thoroughly evaluated. Here we describe validation studies, conducted during daily activities at home, in the outpatient clinic, in the cardiac catheterization laboratory and in the intensive care unit, of the safety and performance of a wearable ultrasound sensor for blood pressure monitoring. The sensor has closely connected sonographic windows and a backing layer that improves the sensor’s accuracy and reliability to meet the highest requirements of clinical standards. The validation results support the clinical use of the sensor.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"62 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673167","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

Endocytic tagging for degradation 内切酶标记降解

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-19 DOI: 10.1038/s41551-024-01293-5

Filipe V. Almeida

引用次数: 0

Ablation of FAS confers allogeneic CD3– CAR T cells with resistance to rejection by T cells and natural killer cells 消融 FAS 使异体 CD3- CAR T 细胞具有抗 T 细胞和自然杀伤细胞排斥的能力

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-18 DOI: 10.1038/s41551-024-01282-8

Silvia Menegatti, Sheila Lopez-Cobo, Aurelien Sutra Del Galy, Jaime Fuentealba, Lisseth Silva, Laetitia Perrin, Sandrine Heurtebise-Chrétien, Valentine Pottez-Jouatte, Aurelie Darbois, Nina Burgdorf, Anne-Laure Privat, Albane Simon, Marguerite Laprie-Sentenac, Michael Saitakis, Bryce Wick, Beau R. Webber, Branden S. Moriarity, Olivier Lantz, Sebastian Amigorena, Laurie Menger

{"title":"Ablation of FAS confers allogeneic CD3– CAR T cells with resistance to rejection by T cells and natural killer cells","authors":"Silvia Menegatti, Sheila Lopez-Cobo, Aurelien Sutra Del Galy, Jaime Fuentealba, Lisseth Silva, Laetitia Perrin, Sandrine Heurtebise-Chrétien, Valentine Pottez-Jouatte, Aurelie Darbois, Nina Burgdorf, Anne-Laure Privat, Albane Simon, Marguerite Laprie-Sentenac, Michael Saitakis, Bryce Wick, Beau R. Webber, Branden S. Moriarity, Olivier Lantz, Sebastian Amigorena, Laurie Menger","doi":"10.1038/s41551-024-01282-8","DOIUrl":"10.1038/s41551-024-01282-8","url":null,"abstract":"Allogeneic chimaeric antigen receptor T cells (allo-CAR T cells) derived from healthy donors could provide rapid access to standardized and affordable batches of therapeutic cells if their rejection by the host’s immune system is avoided. Here, by means of an in vivo genome-wide CRISPR knockout screen, we show that the deletion of Fas or B2m in allo- T cells increases their survival in immunocompetent mice. Human B2M– allo-CAR T cells become highly sensitive to rejection mediated by natural killer (NK) cells, whereas FAS– CAR T cells expressing normal levels of human leukocyte antigen I remain resistant to NK cells. CD3– FAS– CAR T cells outperformed CD3– B2M– CAR T cells in the control of leukaemia growth in mice under allogeneic pressure by T cells and NK cells. The partial protection of CD3– FAS– allo-CAR T cells from cellular rejection may improve the efficacy of allogeneic cellular therapies in patients with cancer. The ablation of FAS and CD3 in allogeneic chimeric antigen receptor T cells confers them with partial protection from rejection by T cells and natural killer cells in immunocompetent hosts.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 12","pages":"1651-1664"},"PeriodicalIF":26.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665501","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

Stress impacts immunity via the gut 压力通过肠道影响免疫力

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-15 DOI: 10.1038/s41551-024-01294-4

Jennifer Haskell

引用次数: 0