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Newcomer anti-IL-33 makes strides in COPD. 新抗il -33在COPD中取得进展。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-05-07 DOI: 10.1038/s41587-026-03136-x
Charlotte Harrison
{"title":"Newcomer anti-IL-33 makes strides in COPD.","authors":"Charlotte Harrison","doi":"10.1038/s41587-026-03136-x","DOIUrl":"https://doi.org/10.1038/s41587-026-03136-x","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thymus renaissance poised to boost health and longevity. 胸腺复兴有望促进健康和长寿。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-05-05 DOI: 10.1038/s41587-026-03137-w
Cormac Sheridan
{"title":"Thymus renaissance poised to boost health and longevity.","authors":"Cormac Sheridan","doi":"10.1038/s41587-026-03137-w","DOIUrl":"https://doi.org/10.1038/s41587-026-03137-w","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A PIVOT towards single-cell functional genetic screening in plants. 植物单细胞功能基因筛选的支点。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-05-05 DOI: 10.1038/s41587-026-03141-0
{"title":"A PIVOT towards single-cell functional genetic screening in plants.","authors":"","doi":"10.1038/s41587-026-03141-0","DOIUrl":"https://doi.org/10.1038/s41587-026-03141-0","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A single-cell screening platform accelerates functional genetics in plants. 单细胞筛选平台加速植物功能遗传学。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-05-05 DOI: 10.1038/s41587-026-03094-4
Tara N Lowensohn, Will B Cody, Chun Tsai, Alexander E Vlahos, Connor C Call, Xiaojing J Gao, Elizabeth S Sattely
{"title":"A single-cell screening platform accelerates functional genetics in plants.","authors":"Tara N Lowensohn, Will B Cody, Chun Tsai, Alexander E Vlahos, Connor C Call, Xiaojing J Gao, Elizabeth S Sattely","doi":"10.1038/s41587-026-03094-4","DOIUrl":"https://doi.org/10.1038/s41587-026-03094-4","url":null,"abstract":"<p><p>Elucidating gene function in highly redundant genetic programs such as signaling pathways is challenging in model and nonmodel plants with current whole-plant genetic screening tools. Many of these challenges could be overcome if screens were instead carried out using individual cells harboring genetic perturbations. Here we report a single-cell screening platform, PIVOT (protoplast isolation after virus overexpression in planta), to accelerate identification and functional characterization of plant genes. We use Nicotiana benthamiana as a heterologous host to test gene libraries arrayed in a single leaf. PIVOT harnesses viral superinfection exclusion to ensure single multiplicity of infection per cell during pooled library delivery. Additionally, we engineer a cell-surface protein as a phenotypic marker for isolating cells of interest from a heterogeneous population. Using this system, we recover regulators of cytokinin signaling from an Arabidopsis open reading frame library. We anticipate PIVOT will be broadly applicable for high-throughput, single-cell functional genetic screening across the plant kingdom.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Digital twins of ex vivo human lungs enable accurate and personalized evaluation of therapeutic efficacy. 离体人肺的数字双胞胎能够准确和个性化地评估治疗效果。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-05-04 DOI: 10.1038/s41587-026-03121-4
Xuanzi Zhou, Bo Wang, Yiyang Wei, Serena Hacker, Sumin Kim, Thomas Borrillo, Abby McCaig, Haaniya Ahmed, Youxue Ren, Olivia Hough, Luca Orsini, Bonnie T Chao, Micheal McInnis, Marcelo Cypel, Mingyao Liu, Jonathan C Yeung, Lorenzo Del Sorbo, Shaf Keshavjee, Andrew T Sage
{"title":"Digital twins of ex vivo human lungs enable accurate and personalized evaluation of therapeutic efficacy.","authors":"Xuanzi Zhou, Bo Wang, Yiyang Wei, Serena Hacker, Sumin Kim, Thomas Borrillo, Abby McCaig, Haaniya Ahmed, Youxue Ren, Olivia Hough, Luca Orsini, Bonnie T Chao, Micheal McInnis, Marcelo Cypel, Mingyao Liu, Jonathan C Yeung, Lorenzo Del Sorbo, Shaf Keshavjee, Andrew T Sage","doi":"10.1038/s41587-026-03121-4","DOIUrl":"https://doi.org/10.1038/s41587-026-03121-4","url":null,"abstract":"<p><p>Digital twins are an emerging concept in healthcare that envisions integration of molecular, physiological, functional and clinical data to create computational models of biological systems such as cells, organs and individuals. However, the lack of large, multimodal datasets has so far precluded the realization of comprehensive digital twins in medicine. Ex vivo lung perfusion (EVLP) allows the study of human lungs outside the body under physiological conditions and generates multimodal data from imaging, physiologic monitoring and molecular assays. Here we report lung digital twins developed from the largest known clinical EVLP dataset. We show that the digital twin framework accurately models >75 parameters spanning lung physiology, biochemistry, radiography, transcriptomics, metabolomics and proteomics. Furthermore, direct comparison to experimental data on EVLP lungs treated with alteplase demonstrates that digital twins can precisely assess therapeutic efficacy. Together, these results establish human lung digital twins developed using EVLP as a data-rich approach to improve the evaluation of therapeutic effects.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TxPert: using multiple knowledge graphs for prediction of transcriptomic perturbation effects. TxPert:使用多个知识图来预测转录组扰动效应。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-05-01 DOI: 10.1038/s41587-026-03113-4
Frederik Wenkel, Wilson Tu, Cassandra Masschelein, Hamed Shirzad, Liam Hodgson, Ihab Bendidi, Cian Eastwood, Shawn T Whitfield, Craig Russell, Yassir El Mesbahi, Jiarui Ding, Marta M Fay, Berton Earnshaw, Emmanuel Noutahi, Alisandra K Denton
{"title":"TxPert: using multiple knowledge graphs for prediction of transcriptomic perturbation effects.","authors":"Frederik Wenkel, Wilson Tu, Cassandra Masschelein, Hamed Shirzad, Liam Hodgson, Ihab Bendidi, Cian Eastwood, Shawn T Whitfield, Craig Russell, Yassir El Mesbahi, Jiarui Ding, Marta M Fay, Berton Earnshaw, Emmanuel Noutahi, Alisandra K Denton","doi":"10.1038/s41587-026-03113-4","DOIUrl":"https://doi.org/10.1038/s41587-026-03113-4","url":null,"abstract":"<p><p>Accurately predicting cellular responses to genetic perturbations is essential for understanding disease mechanisms and designing effective therapies. Yet, exhaustively exploring the space of possible perturbations (for example, multigene perturbations or across tissues and cell types) is prohibitively expensive, motivating methods that can generalize to unseen conditions. We present TxPert, a latent-transfer-based deep learning method that uses multiple knowledge graphs of gene (product)-gene (product) relationships to predict transcriptomic perturbation effects. Different knowledge graphs encode complementary information and we show that a combination of graphs derived from biological databases and high-throughput perturbation screens yields the best performance. For predictions of single unseen perturbations, TxPert approaches the performance of split-half experimental reproducibility. For double unseen perturbations and single perturbations in a different cell line, its predictions increase Person Δ for unseen single perturbations by 8-25% over existing methods.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA-guided CRISPR-Cas12a effectors for programmable RNA recognition and cleavage. 用于可编程RNA识别和切割的dna引导CRISPR-Cas12a效应物。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-05-01 DOI: 10.1038/s41587-026-03120-5
Xiaolong Wu, Wai Hei Lam, Zibin Zhao, Yumeng Cao, Haosi Lin, Xianzhen Feng, Yuanliang Zhai, I-Ming Hsing
{"title":"DNA-guided CRISPR-Cas12a effectors for programmable RNA recognition and cleavage.","authors":"Xiaolong Wu, Wai Hei Lam, Zibin Zhao, Yumeng Cao, Haosi Lin, Xianzhen Feng, Yuanliang Zhai, I-Ming Hsing","doi":"10.1038/s41587-026-03120-5","DOIUrl":"https://doi.org/10.1038/s41587-026-03120-5","url":null,"abstract":"<p><p>CRISPR-Cas effectors typically rely on RNA guides to recognize target sequences. In Cas12a, the protospacer adjacent motif on DNA engages conserved protein residues, triggering target binding and nuclease activation. Here we reprogram Cas12a into a DNA-guided, RNA-targeting effector. Exploiting protospacer-adjacent motif-dependent interaction, we engineer synthetic CRISPR DNA that engages Cas12a to form a functional deoxyribonucleoprotein complex, while repurposing solely RNA as the programmable target. Structural, biophysical and biochemical analyses reveal the molecular basis of this DNA-guided, RNA-targeting configuration and support an activation pathway distinct from that of canonical RNA-guided systems. DNA-guided Cas12a enables direct RNA detection and efficient intracellular RNA knockdown, establishing a modular activation architecture for CRISPR-Cas12a and expanding the design space for programmable RNA manipulation.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tracing the rise of biomedical foundation models. 追踪生物医学基础模型的兴起。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-04-30 DOI: 10.1038/s41587-026-03135-y
Yuzhou Chang, Hao Cheng, Mirage Modi, Guangyu Wang, Dong Xu, Qin Ma
{"title":"Tracing the rise of biomedical foundation models.","authors":"Yuzhou Chang, Hao Cheng, Mirage Modi, Guangyu Wang, Dong Xu, Qin Ma","doi":"10.1038/s41587-026-03135-y","DOIUrl":"https://doi.org/10.1038/s41587-026-03135-y","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tuning the immune response to mRNA vaccines. 调整对mRNA疫苗的免疫反应。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-04-29 DOI: 10.1038/s41587-026-03125-0
Haseeb Mughal, Yizong Hu, Daniel G Anderson
{"title":"Tuning the immune response to mRNA vaccines.","authors":"Haseeb Mughal, Yizong Hu, Daniel G Anderson","doi":"10.1038/s41587-026-03125-0","DOIUrl":"https://doi.org/10.1038/s41587-026-03125-0","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression. mRNA疫苗免疫通过肝细胞脱靶而增强,不依赖于树突状细胞的表达。
IF 41.7 1区 生物学
Nature biotechnology Pub Date : 2026-04-29 DOI: 10.1038/s41587-026-03099-z
Adam Marks, Sophia Siu, Filippo Bianchini, Chunxi Wang, Ashwitha Lakshmi, Matthew Phelan, Andrew Zhu, Chang Moon, Judit Morla-Folch, Abraham J P Teunissen, Angelo Amabile, Alessia Baccarini, Miriam Merad, Joshua D Brody, Yizhou Dong, Brian D Brown
{"title":"mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression.","authors":"Adam Marks, Sophia Siu, Filippo Bianchini, Chunxi Wang, Ashwitha Lakshmi, Matthew Phelan, Andrew Zhu, Chang Moon, Judit Morla-Folch, Abraham J P Teunissen, Angelo Amabile, Alessia Baccarini, Miriam Merad, Joshua D Brody, Yizhou Dong, Brian D Brown","doi":"10.1038/s41587-026-03099-z","DOIUrl":"https://doi.org/10.1038/s41587-026-03099-z","url":null,"abstract":"<p><p>Proteins encoded by mRNA vaccines can be expressed by a diversity of transfected cell types but how cell-type-specific expression influences immunity is poorly understood. To investigate this, we incorporated synthetic microRNA target sites (miRT) into lipid nanoparticle (LNP)-delivered mRNA vaccines to silence mRNA expression specifically in professional antigen-presenting cells (pAPCs), hepatocytes or myocytes. We found that mRNA expression in pAPCs was dispensable for priming antigen-specific T cells, whereas mRNA expression in myocytes induced similar or stronger immune responses, including for SARS-CoV-2, suggesting that antigen cross-presentation or cross-dressing may be more impactful than direct mRNA expression in pAPCs. In contrast, mRNA expression in hepatocytes suppressed the antigen-specific T cell response, partly through PD1/PDL1. In mice bearing tumor-associated antigen (TAA)-expressing lymphoma cells, miRT-mediated hepatocyte-silenced TAA mRNA vaccine enhanced immune response and reduced tumor burden. Thus, non-pAPC expression shapes immunity to mRNA-encoded protein and inclusion of miRTs can boost or blunt mRNA-LNP immunogenicity.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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