Nature biotechnology最新文献_第8页

Enhanced antitumor immunity of mRNA vaccines by bioorthogonal-like delayed activation of exogeneous STING 外源性STING生物正交样延迟激活增强mRNA疫苗抗肿瘤免疫

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-08-19 DOI: 10.1038/s41587-026-03224-y

Pengxia Qin, Qiushi Qin, Yanyun Hao, Ming Liu, Yijia Li, Yunxuan Liu, Ziqiong Jiang, Tao Ma, Weixue Wang, Yu Hou, Ruochuan Liu, Yajuan Wang, Buyao Li, Xiaorong Guo, Kun Wang, Pengting Zhang, Zhiqiang Zhao, Baocai Xing, Bin Ma, Yinuo Wang, Ning Zhang, Chuanhui Han, Lei Miao

{"title":"Enhanced antitumor immunity of mRNA vaccines by bioorthogonal-like delayed activation of exogeneous STING","authors":"Pengxia Qin, Qiushi Qin, Yanyun Hao, Ming Liu, Yijia Li, Yunxuan Liu, Ziqiong Jiang, Tao Ma, Weixue Wang, Yu Hou, Ruochuan Liu, Yajuan Wang, Buyao Li, Xiaorong Guo, Kun Wang, Pengting Zhang, Zhiqiang Zhao, Baocai Xing, Bin Ma, Yinuo Wang, Ning Zhang, Chuanhui Han, Lei Miao","doi":"10.1038/s41587-026-03224-y","DOIUrl":"https://doi.org/10.1038/s41587-026-03224-y","url":null,"abstract":"The development of cGAS–STING (stimulator of interferon genes) agonists as mRNA vaccine adjuvants has been hampered by widespread STING expression and by the observation that codelivered STING agonists suppress antigen mRNA translation. Here, to address these challenges, we engineer synchronized STING (Syn-STING): a lipid nanoparticle (LNP) codelivering antigen mRNA, mRNA encoding full-length STING transmembrane protein and a bioorthogonal-like delayed-release STING activator, DMXAA. DMXAA release is controlled by a biodegradable linker, enabling localized mouse STING activation while avoiding systemic endogeneous human STING recognition. In humanized STING mouse models, we test human papillomavirus E7 and ovalbumin antigens with mouse STING or a human STING mutant engineered for DMXAA specificity. Intratumoral or subcutaneous LNPs are preferentially internalized by myeloid cells, preserving antigen expression fidelity, achieving localized STING activation in antigen-presenting cells and preventing systemic regulatory B cell differentiation and immunocyte apoptosis. The Syn-STING vaccine elicits robust adaptive responses and Th1-biased T cell immunity. It suppresses tumor growth and prolongs survival while exhibiting negligible anti-STING immunity.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"70 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769245","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

Author Correction: Derivation of embryonic stem cells across avian species. 作者更正：禽类胚胎干细胞的衍生。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-19 DOI: 10.1038/s41587-026-03309-8

Xi Chen, Zheng Guo, Xinyi Tong, Xizi Wang, Xugeng Liu, Hiroki Nagai, Ping Wu, Jiayi Lu, David Huss, Martin Tran, Carol Readhead, Christina Wu, Lin Cao, Yixin Huang, Zhaohan Zeng, Fan Feng, Nima Adhami, Sirjan Mor, Rusty Lansford, Cheng-Ming Chuong, Guojun Sheng, Carlos Lois, Qi-Long Ying

引用次数: 0

Lessons from drug revenue life cycles: distributions across modalities and therapeutic areas 药物收入生命周期的经验教训：跨模式和治疗领域的分布。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-18 DOI: 10.1038/s41587-026-03278-y

Matthew Vogel, Zander Cowan, Amitabh Chandra

引用次数: 0

Editor’s pick: Dispatch Biotherapeutics 编者精选：《派遣生物疗法》。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-18 DOI: 10.1038/s41587-026-03293-z

Ken Garber

引用次数: 0

A scalable platform to discover and characterize substrates of molecular glue degraders. 一个可扩展的平台来发现和表征分子胶水降解剂的底物。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-17 DOI: 10.1038/s41587-026-03256-4

引用次数: 0

Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells 病毒样颗粒能够在原代人髓细胞中进行靶向基因工程和聚合CRISPR筛选

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-08-17 DOI: 10.1038/s41587-026-03258-2

Hyuncheol Jung, Pascal Devant, Carter Ching, Mineto Ota, Emma Dann, Ronghui Zhu, Chandrima Modak, Ana Vasquez-Ibarra, Jennifer R. Hamilton, Zachary Steinhart, Wayne Ngo, Luis Sandoval, Jae Hyung Jung, Jae Hyun J. Lee, Da Xu, Meirui An, Esha Urs, Peixin Amy Chen, Vincent Allain, Takuya Tada, Luke A. Gilbert, Brian R. Shy, Jonathan K. Pritchard, James K. Nuñez, Nathaniel R. Landau, David R. Liu, Justin Eyquem, Jennifer A. Doudna, Alexander Marson, Julia Carnevale

{"title":"Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells","authors":"Hyuncheol Jung, Pascal Devant, Carter Ching, Mineto Ota, Emma Dann, Ronghui Zhu, Chandrima Modak, Ana Vasquez-Ibarra, Jennifer R. Hamilton, Zachary Steinhart, Wayne Ngo, Luis Sandoval, Jae Hyung Jung, Jae Hyun J. Lee, Da Xu, Meirui An, Esha Urs, Peixin Amy Chen, Vincent Allain, Takuya Tada, Luke A. Gilbert, Brian R. Shy, Jonathan K. Pritchard, James K. Nuñez, Nathaniel R. Landau, David R. Liu, Justin Eyquem, Jennifer A. Doudna, Alexander Marson, Julia Carnevale","doi":"10.1038/s41587-026-03258-2","DOIUrl":"https://doi.org/10.1038/s41587-026-03258-2","url":null,"abstract":"Primary human myeloid cells hold promise for immunotherapies, yet efficient, scalable technologies for engineering and screening in these cells remain limited. Here we present a virus-like particle (VLP)-based toolkit that delivers diverse CRISPR editing modalities to human monocytes, macrophages and dendritic cells with high efficiency while preserving viability and innate immune responsiveness. VLP-mediated delivery of ribonucleoproteins supports gene knockout, base editing and epigenetic silencing. Combined with adeno-associated virus-mediated donor delivery, this approach enables site-specific integration of large DNA sequences by homology-directed repair. We developed SLICeVLP, which pairs sgRNA delivery by VPX-lentivirus with Cas9 protein delivery by engineered VLPs, and used it for pooled loss-of-function and Perturb-seq screens in human macrophages. We uncovered regulators of tumor necrosis factor (TNF) and CD80 expression, converging on TNFAIP3 as a central regulator of inflammatory polarization. TNFAIP3 ablation drove a proinflammatory state resistant to suppressive repolarization and enhanced cytotoxicity in chimeric antigen receptor macrophages. This system enables unbiased functional genomics in primary human myeloid cells, with implications for myeloid cell therapy design.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"70 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769129","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

Characterization of microbial dark matter at scale with MetaSBT and taxonomy-aware Sequence Bloom Trees 利用MetaSBT和分类敏感序列开花树在规模上表征微生物暗物质

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-08-13 DOI: 10.1038/s41587-026-03245-7

Fabio Cumbo, Daniel Blankenberg

{"title":"Characterization of microbial dark matter at scale with MetaSBT and taxonomy-aware Sequence Bloom Trees","authors":"Fabio Cumbo, Daniel Blankenberg","doi":"10.1038/s41587-026-03245-7","DOIUrl":"https://doi.org/10.1038/s41587-026-03245-7","url":null,"abstract":"Accurately characterizing metagenome-assembled genomes remains a substantial challenge due to the presence of sequencing errors, incomplete assembly and contamination. Here, we present MetaSBT, a tool for organizing, indexing and characterizing microbial reference genomes and metagenome-assembled genomes, demonstrated in this study using viruses. MetaSBT identifies clusters of genomes across all seven taxonomic levels using the Sequence Bloom Tree data structure, which relies on Bloom filters to index large amounts of genomes based on their k-mer composition. We built an initial set of databases composed of over 190,000 viral genomes from public sources, grouped into sequence-consistent clusters at different taxonomic levels. We defined over 40,000 candidate species, ~80% of which, to our knowledge, do not match viral species in reference databases to date. Furthermore, we showed that our databases are useful to existing quantitative metagenomic profilers to unlock the detection of unknown microbes and the estimation of their abundance in metagenomic samples. The open-source framework and databases are fully integrated into the Galaxy platform.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"35 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728866","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

Proteome-wide identification of the druggable CRBN interactome 可用药的CRBN相互作用组的全蛋白质组鉴定

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-08-13 DOI: 10.1038/s41587-026-03237-7

Pius Galli, Shuhao Xiao (肖书豪), Yanxiang Meng, Alexander Hanzl, Alexandra M. Bendel, Regina Baur, Jacob D. Aguirre, Anna M. Diaz-Rovira, Maximilian R. Stammnitz, Georg Kempf, Lukas Kater, Kenji Shimada, Ye Wei (韦业), Andreas Scheck, Dominique Klein, Simone Cavadini, Ben Lehner, Guillaume Diss, Bruno E. Correia, Nicolas H. Thomä

{"title":"Proteome-wide identification of the druggable CRBN interactome","authors":"Pius Galli, Shuhao Xiao \u0000 (肖书豪), Yanxiang Meng, Alexander Hanzl, Alexandra M. Bendel, Regina Baur, Jacob D. Aguirre, Anna M. Diaz-Rovira, Maximilian R. Stammnitz, Georg Kempf, Lukas Kater, Kenji Shimada, Ye Wei \u0000 (韦业), Andreas Scheck, Dominique Klein, Simone Cavadini, Ben Lehner, Guillaume Diss, Bruno E. Correia, Nicolas H. Thomä","doi":"10.1038/s41587-026-03237-7","DOIUrl":"https://doi.org/10.1038/s41587-026-03237-7","url":null,"abstract":"Molecular glue degraders (MGDs), such as pomalidomide, induce degradation of non-native substrates by the cullin-RING E3 ligase 4 (CRL4) through its substrate receptor cereblon (CRBN). Here, to explore CRBN programmability, we tested whether reported CRBN–MGD substrates are part of a network of latent CRBN interactors, proteins capable of MGD-induced CRBN binding without detectable degradation. Leveraging a highly parallel protein complementation assay (GluePCA) to measure MGD-induced interaction between CRBN and zinc fingers, we identified ~210 zinc fingers bound to CRBN–pomalidomide, where top binders are already reported as degraded by dedicated MGDs. To map latent CRBN–MGD interactions proteome-wide and define the accessible CRBN interaction space, we combined artificial intelligence-derived protein surface queries (MaSIF-mimicry) with GluePCA. This pipeline identified 6 known and 43 novel CRBN–pomalidomide binders, including orthogonally validated hits. We find that these binders provide privileged starting points for MGD development. We expect this binding-focused workflow to be applicable to other MGD–E3 ligase systems, potentially extending the scope of this emerging drug class.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"161 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148729043","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

Simultaneous single-cell profiling of chromatin, transcriptome and surface markers with OneCell CUT&Tag captures epigenomic reprogramming. 同时单细胞分析染色质，转录组和表面标记与OneCell CUT&Tag捕获表观基因组重编程。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-12 DOI: 10.1038/s41587-026-03259-1

Anna Schwager, Eve Moutaux, Adeline Durand, Alexandra Van Keymeulen, Amélie Viaene, Mélanie Miranda, Louisa Hadj Abed, Simon Besson-Girard, Marion Lambault, Délia Dupré, Grégoire Jouault, Melissa Saichi, Juliette Bertorello, Simon Dumas, Mathias Schwartz, Marthe Laisné, Justine Marsolier, Manuel Guthmann, Lorraine Bonneville, Urvashi Chitnavis, Déborah Bourc'his, Elisabetta Marangoni, Nicolas Servant, Cédric Blanpain, Leïla Perié, Céline Vallot

{"title":"Simultaneous single-cell profiling of chromatin, transcriptome and surface markers with OneCell CUT&Tag captures epigenomic reprogramming.","authors":"Anna Schwager, Eve Moutaux, Adeline Durand, Alexandra Van Keymeulen, Amélie Viaene, Mélanie Miranda, Louisa Hadj Abed, Simon Besson-Girard, Marion Lambault, Délia Dupré, Grégoire Jouault, Melissa Saichi, Juliette Bertorello, Simon Dumas, Mathias Schwartz, Marthe Laisné, Justine Marsolier, Manuel Guthmann, Lorraine Bonneville, Urvashi Chitnavis, Déborah Bourc'his, Elisabetta Marangoni, Nicolas Servant, Cédric Blanpain, Leïla Perié, Céline Vallot","doi":"10.1038/s41587-026-03259-1","DOIUrl":"10.1038/s41587-026-03259-1","url":null,"abstract":"<p><p>Simultaneous mapping of chromatin states and transcriptomes in rare cell populations is challenging, as most methods require thousands of cells and are limited in their ability to capture multiple molecular layers accurately within the same cell. Here we introduce OneCell CUT&Tag, a method that provides matched high-resolution epigenome, full-transcriptome and surface marker quantification from every cell, with input as low as one cell, without relying on computational aggregation into metacells. Using this approach, we uncover epigenomic priming of basal cells in the mammary gland and capture the dynamics of basal-to-luminal transdifferentiation, suggesting that epigenomic and transcriptional remodeling do not occur in complete synchrony during cell-fate conversion. Adaptable to diverse samples and tissues, this method also reveals the role of H3K27me3 in shaping zygotic expression programs. By matching multiple layers of molecular information within individual cells, OneCell CUT&Tag reveals how complementary regulatory layers shape cellular identity and state, enabling the study of rare biological samples in development and disease.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727452","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

Author Correction: Circular RNA aptamers targeting neuroinflammation ameliorate Alzheimer disease phenotypes in mouse models. 作者更正：靶向神经炎症的环状RNA适体改善了小鼠模型中的阿尔茨海默病表型。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-12 DOI: 10.1038/s41587-026-03281-3

Xin Feng, Bo-Wen Jiang, Si-Nan Zhai, Chu-Xiao Liu, Hao Wu, Bang-Qi Zhu, Meng-Yuan Wei, Jia Wei, Li Yang, Ling-Ling Chen

引用次数: 0