Nature biotechnology最新文献_第9页

BBB Hunter agent nears FDA decision BBB Hunter代理商接近FDA的决定。

IF 41.7 1区生物学

Nature biotechnology Pub Date : 2026-03-17 DOI: 10.1038/s41587-026-03066-8

引用次数: 0

30 years of Nature Biotechnology 30年的自然生物技术。

IF 41.7 1区生物学

Nature biotechnology Pub Date : 2026-03-17 DOI: 10.1038/s41587-026-03073-9

引用次数: 0

Biotech news from around the world 来自世界各地的生物技术新闻。

IF 41.7 1区生物学

Nature biotechnology Pub Date : 2026-03-17 DOI: 10.1038/s41587-026-03063-x

引用次数: 0

AI turbocharges antibody hunt for binders with drug-like qualities 人工智能加速了抗体寻找具有药物性质的粘合剂。

IF 41.7 1区生物学

Nature biotechnology Pub Date : 2026-03-17 DOI: 10.1038/s41587-026-03048-w

Andrew Marshall

引用次数: 0

A logic-gated trispecific engager enhances macrophage killing of cancer cells in solid tumors. 逻辑门控三特异性接合物增强实体肿瘤中巨噬细胞对癌细胞的杀伤。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-03-13 DOI: 10.1038/s41587-026-03057-9

Xiaotian Zhao,Weiqiang Jing,Ganyu Wang,Zhanyan Liu,Xinxin Xu,Maosen Han,Zhipeng Fu,Yulin Zhang,Zuolin Zheng,Jing Zhang,Longyu Bo,Xianghui Dong,Caiping Li,Yanhua Sun,Junfeng Zhang,Fabao Zhao,Nianzeng Xing,Kun Zhao,Xinyi Jiang

{"title":"A logic-gated trispecific engager enhances macrophage killing of cancer cells in solid tumors.","authors":"Xiaotian Zhao,Weiqiang Jing,Ganyu Wang,Zhanyan Liu,Xinxin Xu,Maosen Han,Zhipeng Fu,Yulin Zhang,Zuolin Zheng,Jing Zhang,Longyu Bo,Xianghui Dong,Caiping Li,Yanhua Sun,Junfeng Zhang,Fabao Zhao,Nianzeng Xing,Kun Zhao,Xinyi Jiang","doi":"10.1038/s41587-026-03057-9","DOIUrl":"https://doi.org/10.1038/s41587-026-03057-9","url":null,"abstract":"The antitumor efficacy of immune cell engagers that bind two targets on the same immune cell is limited by structural constraints, leading to incomplete coengagement and uncoordinated signaling. Here, we develop a trispecific macrophage engager (TrME) that both activates the prophagocytic receptor lipoprotein receptor-related protein 1 (LRP1) and blocks the antiphagocytic receptor signal regulatory protein alpha (SIRPα). This 'activate and block' AND logic gate, when coupled to a tumor-targeting moiety, enables coordinated signaling that enhances macrophage cytotoxicity against solid tumors. The TrME tandemly links monovalent LRP1 activator calreticulin, anti-SIRPα scFv and a tumor-associated antigen (TAA)-targeting arm through flexible linkers. Computational modeling and screening of tandem constructs revealed an optimal conformation for robust cis-targeting, allowing logic-gated control of ratiometric prophagocytic and antiphagocytic signaling. In situ generation of TrME by delivering mRNA encoding TAA-targeting TrME through an optimized lipid nanoparticle system activates macrophages and induces antitumor responses, significantly inhibiting tumor growth and prolonging survival in multiple solid tumor mouse models.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"95 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446880","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

Biomolecular profiling for noninvasive health monitoring. 无创健康监测的生物分子分析。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-03-12 DOI: 10.1038/s41587-026-03050-2

Moon-Ju Kim,José A Lasalde-Ramírez,Wenzheng Heng,Wei Gao

{"title":"Biomolecular profiling for noninvasive health monitoring.","authors":"Moon-Ju Kim,José A Lasalde-Ramírez,Wenzheng Heng,Wei Gao","doi":"10.1038/s41587-026-03050-2","DOIUrl":"https://doi.org/10.1038/s41587-026-03050-2","url":null,"abstract":"Biomolecular profiling offers a powerful lens into human physiology, yet current diagnostics often rely on invasive sampling and delayed, centralized analysis. Advances in mass spectrometry (MS), particularly untargeted metabolomics and proteomics, have expanded molecular access to noninvasive biofluids such as sweat, saliva, tears and interstitial fluid, revealing dynamic biomarkers linked to both chronic and acute conditions. In parallel, wearable biosensors enable real-time, on-body chemical sensing, but remain limited to a narrow panel of predefined analytes. This Review highlights how MS-based molecular discovery and wearable sensing serve as complementary approaches-MS enabling high-dimensional untargeted profiling and wearables delivering longitudinal real-time data-and also discusses how their bidirectional integration and co-evolution open new possibilities for personalized noninvasive health monitoring. We discuss advances in sampling strategies, sensing modalities and system integration, and outline criteria for identifying biomarkers amenable to sensor translation. By uniting untargeted discovery with real-world deployment, this convergence shifts personalized noninvasive healthcare from episodic diagnostics to continuous, context-aware monitoring.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"33 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439438","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

Quantifying endosomal escape in vivo to guide lipid nanoparticle design. 定量体内内体逃逸以指导脂质纳米颗粒设计。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-03-11 DOI: 10.1038/s41587-026-03047-x

Zhengwei Liu,Yizhou Dong

引用次数: 0

In vivo endosomal escape assay identifies mechanisms for efficient hepatic LNP delivery. 体内内体逃逸试验确定了有效的肝脏LNP递送机制。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-03-11 DOI: 10.1038/s41587-026-03022-6

Antony Jozić,Chloé Le Roux,Jeonghwan Kim,Mathieu Berchel,Deepak Kumar Sahel,Emily K Bodi,Michelle Palumbo,Aishwarya Vasudevan,Namratha Turuvekere Vittala Murthy,Yulia Eygeris,Milan Gautam,Elissa Bloom,Anthony P Barnes,Paul-Alain Jaffrès,Gaurav Sahay

{"title":"In vivo endosomal escape assay identifies mechanisms for efficient hepatic LNP delivery.","authors":"Antony Jozić,Chloé Le Roux,Jeonghwan Kim,Mathieu Berchel,Deepak Kumar Sahel,Emily K Bodi,Michelle Palumbo,Aishwarya Vasudevan,Namratha Turuvekere Vittala Murthy,Yulia Eygeris,Milan Gautam,Elissa Bloom,Anthony P Barnes,Paul-Alain Jaffrès,Gaurav Sahay","doi":"10.1038/s41587-026-03022-6","DOIUrl":"https://doi.org/10.1038/s41587-026-03022-6","url":null,"abstract":"Endosomal escape is a central barrier to efficient nucleic acid delivery by lipid nanoparticles (LNPs) and remains challenging to quantify in vivo. We report a library of branched ionizable phospholipids that markedly enhance messenger RNA delivery to the liver. The lead candidate BiP-20 outperformed the clinical benchmark LP01 by eightfold for CRISPR-Cas9 editing of the TTR gene at low dose with rapid pharmacokinetics. To quantify the endosomal escape kinetics of BiP-20, we used LysoTag mice, which allow immunoisolation of liver lysosomes, and our Lysosomal Barcoding method, finding that ~8% of BiP-20 LNPs reach the cytosol within 30 min of administration. Lysosomal proteomics revealed mechanistic regulators of escape and BiP-20-induced alterations in endosomal maturation and recycling pathways. Loss of Rab7, a mediator of late endosomal maturation, increased LNP escape. These findings provide a potent class of ionizable lipids for RNA delivery, a method to quantify endosomal escape in vivo, and mechanistic insight into the endolysosomal determinants of LNP trafficking.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"30 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393855","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

Engineered TnpB genome editors for plants and human cells identified by ribonucleoprotein mutational scanning. 核糖核蛋白突变扫描鉴定的植物和人类细胞TnpB基因组编辑器。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-03-11 DOI: 10.1038/s41587-026-03059-7

Brittney W Thornton,Rachel F Weissman,Jorge E Rodriguez,Ryan V Tran,Brenda T Duong,Cynthia I Terrace,Ugrappa Nagalakshmi,George Austin,Evan D Groover,Flora Zhiqi Wang,Jung-Un Park,Viktoriya Georgieva,Julia Tartaglia,Myeong-Je Cho,Savithramma P Dinesh-Kumar,Jennifer A Doudna,David F Savage

{"title":"Engineered TnpB genome editors for plants and human cells identified by ribonucleoprotein mutational scanning.","authors":"Brittney W Thornton,Rachel F Weissman,Jorge E Rodriguez,Ryan V Tran,Brenda T Duong,Cynthia I Terrace,Ugrappa Nagalakshmi,George Austin,Evan D Groover,Flora Zhiqi Wang,Jung-Un Park,Viktoriya Georgieva,Julia Tartaglia,Myeong-Je Cho,Savithramma P Dinesh-Kumar,Jennifer A Doudna,David F Savage","doi":"10.1038/s41587-026-03059-7","DOIUrl":"https://doi.org/10.1038/s41587-026-03059-7","url":null,"abstract":"TnpB is a diverse family of RNA-guided endonucleases associated with prokaryotic transposons. Because of their small size and putative evolutionary relationship to CRISPR-Cas12, TnpB enzymes hold great potential for genome editing. However, most TnpBs lack robust gene-editing activity. Here, we mapped comprehensive sequence-function landscapes of a TnpB ribonucleoprotein using deep mutational scanning and we discovered activating mutations in both the RNA and the protein. Leveraging the protein's mutational landscape, we constructed a combinatorial library of activating mutations, from which we identified two enhanced TnpB variants. These variants increased editing in human cells, Nicotania benthamiana, pepper and rice. While editing efficiencies varied by target site, engineered variants achieved up to 55% insertion and deletion frequencies (a 50-fold increase over wild type) in N. benthamiana, surpassing ISYmu1 (<7%), AsCas12f-HKRA (<9%) and other compact editors. These findings highlight elements critical for regulating TnpB endonuclease activity and demonstrate latent activity accessible through mutation.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"9 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393852","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

The promises and challenges of neoantigen cancer vaccines. 新抗原癌症疫苗的前景和挑战。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-03-10 DOI: 10.1038/s41587-026-03018-2

Patrick A Ott

引用次数: 0