Nature biotechnology最新文献_第7页

AI meets real-world patients 人工智能与现实世界中的病人

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-10-07 DOI: 10.1038/s41587-024-02455-1

引用次数: 0

Amplifying mutational profiling of extracellular vesicle mRNA with SCOPE 利用 SCOPE 放大细胞外囊泡 mRNA 的突变图谱

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-07 DOI: 10.1038/s41587-024-02426-6

Jayeon Song, Mi Hyeon Cho, Hayoung Cho, Younseong Song, Sung Woon Lee, Ho Chul Nam, Tae Ho Yoon, Jong Cheol Shin, Jae-Sang Hong, Yejin Kim, Emil Ekanayake, Jueun Jeon, Dong Gil You, Sung Gap Im, Gyu-Seog Choi, Jun Seok Park, Bob C. Carter, Leonora Balaj, An Na Seo, Miles A. Miller, Soo Yeun Park, Taejoon Kang, Cesar M. Castro, Hakho Lee

{"title":"Amplifying mutational profiling of extracellular vesicle mRNA with SCOPE","authors":"Jayeon Song, Mi Hyeon Cho, Hayoung Cho, Younseong Song, Sung Woon Lee, Ho Chul Nam, Tae Ho Yoon, Jong Cheol Shin, Jae-Sang Hong, Yejin Kim, Emil Ekanayake, Jueun Jeon, Dong Gil You, Sung Gap Im, Gyu-Seog Choi, Jun Seok Park, Bob C. Carter, Leonora Balaj, An Na Seo, Miles A. Miller, Soo Yeun Park, Taejoon Kang, Cesar M. Castro, Hakho Lee","doi":"10.1038/s41587-024-02426-6","DOIUrl":"https://doi.org/10.1038/s41587-024-02426-6","url":null,"abstract":"Sequencing of messenger RNA (mRNA) found in extracellular vesicles (EVs) in liquid biopsies can provide clinical information such as somatic mutations, resistance profiles and tumor recurrence. Despite this, EV mRNA remains underused due to its low abundance in liquid biopsies, and large sample volumes or specialized techniques for analysis are required. Here we introduce Self-amplified and CRISPR-aided Operation to Profile EVs (SCOPE), a platform for EV mRNA detection. SCOPE leverages CRISPR-mediated recognition of target RNA using Cas13 to initiate replication and signal amplification, achieving a sub-attomolar detection limit while maintaining single-nucleotide resolution. As a proof of concept, we designed probes for key mutations in KRAS, BRAF, EGFR and IDH1 genes, optimized protocols for single-pot assays and implemented an automated device for multi-sample detection. We validated SCOPE’s ability to detect early-stage lung cancer in animal models, monitored tumor mutational burden in patients with colorectal cancer and stratified patients with glioblastoma. SCOPE can expedite readouts, augmenting the clinical use of EVs in precision oncology.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383682","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

Publisher Correction: Multistate and functional protein design using RoseTTAFold sequence space diffusion 出版商更正：利用 RoseTTAFold 序列空间扩散进行多态和功能蛋白质设计

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-07 DOI: 10.1038/s41587-024-02456-0

Sidney Lyayuga Lisanza, Jacob Merle Gershon, Samuel W. K. Tipps, Jeremiah Nelson Sims, Lucas Arnoldt, Samuel J. Hendel, Miriam K. Simma, Ge Liu, Muna Yase, Hongwei Wu, Claire D. Tharp, Xinting Li, Alex Kang, Evans Brackenbrough, Asim K. Bera, Stacey Gerben, Bruce J. Wittmann, Andrew C. McShan, David Baker

引用次数: 0

A CRISPR-based method for detecting mRNA in extracellular vesicles 基于 CRISPR 的细胞外囊泡 mRNA 检测方法

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-07 DOI: 10.1038/s41587-024-02440-8

引用次数: 0

Advances in optical pooled screening to map spatial complexity 用于绘制空间复杂性图谱的光学集合筛选技术取得进展

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-07 DOI: 10.1038/s41587-024-02434-6

Maurice Kahnwald, Marius Mählen, Koen C. Oost, Prisca Liberali

引用次数: 0

Multiplexed, image-based pooled screens in primary cells and tissues with PerturbView 利用 PerturbView 对原代细胞和组织进行基于图像的多重集合筛选

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-07 DOI: 10.1038/s41587-024-02391-0

Takamasa Kudo, Ana M. Meireles, Reuben Moncada, Yushu Chen, Ping Wu, Joshua Gould, Xiaoyu Hu, Opher Kornfeld, Rajiv Jesudason, Conrad Foo, Burkhard Höckendorf, Hector Corrada Bravo, Jason P. Town, Runmin Wei, Antonio Rios, Vineethkrishna Chandrasekar, Melanie Heinlein, Amy S. Chuong, Shuangyi Cai, Cherry Sakura Lu, Paula Coelho, Monika Mis, Cemre Celen, Noelyn Kljavin, Jian Jiang, David Richmond, Pratiksha Thakore, Elia Benito-Gutiérrez, Kathryn Geiger-Schuller, Jose Sergio Hleap, Nobuhiko Kayagaki, Felipe de Sousa e Melo, Lisa McGinnis, Bo Li, Avtar Singh, Levi Garraway, Orit Rozenblatt-Rosen, Aviv Regev, Eric Lubeck

{"title":"Multiplexed, image-based pooled screens in primary cells and tissues with PerturbView","authors":"Takamasa Kudo, Ana M. Meireles, Reuben Moncada, Yushu Chen, Ping Wu, Joshua Gould, Xiaoyu Hu, Opher Kornfeld, Rajiv Jesudason, Conrad Foo, Burkhard Höckendorf, Hector Corrada Bravo, Jason P. Town, Runmin Wei, Antonio Rios, Vineethkrishna Chandrasekar, Melanie Heinlein, Amy S. Chuong, Shuangyi Cai, Cherry Sakura Lu, Paula Coelho, Monika Mis, Cemre Celen, Noelyn Kljavin, Jian Jiang, David Richmond, Pratiksha Thakore, Elia Benito-Gutiérrez, Kathryn Geiger-Schuller, Jose Sergio Hleap, Nobuhiko Kayagaki, Felipe de Sousa e Melo, Lisa McGinnis, Bo Li, Avtar Singh, Levi Garraway, Orit Rozenblatt-Rosen, Aviv Regev, Eric Lubeck","doi":"10.1038/s41587-024-02391-0","DOIUrl":"https://doi.org/10.1038/s41587-024-02391-0","url":null,"abstract":"Optical pooled screening (OPS) is a scalable method for linking image-based phenotypes with cellular perturbations. However, it has thus far been restricted to relatively low-plex phenotypic readouts in cancer cell lines in culture due to limitations associated with in situ sequencing of perturbation barcodes. Here, we develop PerturbView, an OPS technology that leverages in vitro transcription to amplify barcodes before in situ sequencing, enabling screens with highly multiplexed phenotypic readouts across diverse systems, including primary cells and tissues. We demonstrate PerturbView in induced pluripotent stem cell-derived neurons, primary immune cells and tumor tissue sections from animal models. In a screen of immune signaling pathways in primary bone marrow-derived macrophages, PerturbView uncovered both known and novel regulators of NF-κB signaling. Furthermore, we combine PerturbView with spatial transcriptomics in tissue sections from a mouse xenograft model, paving the way to in situ screens with rich optical and transcriptomic phenotypes. PerturbView broadens the scope of OPS to a wide range of models and applications.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383683","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

Bacteria displaying cytokines heat up the tumor microenvironment 显示细胞因子的细菌使肿瘤微环境升温

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-04 DOI: 10.1038/s41587-024-02429-3

Marine Fidelle, Laurence Zitvogel

引用次数: 0

Non-pathogenic E. coli displaying decoy-resistant IL18 mutein boosts anti-tumor and CAR NK cell responses 显示抗诱饵 IL18 静音蛋白的非致病性大肠杆菌可增强抗肿瘤和 CAR NK 细胞反应

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-04 DOI: 10.1038/s41587-024-02418-6

Shaobo Yang, Michal Sheffer, Isabel E. Kaplan, Zongqi Wang, Mubin Tarannum, Khanhlinh Dinh, Yasmin Abdulhamid, Eden Bobilev, Roman Shapiro, Rebecca Porter, Robert Soiffer, Jerome Ritz, John Koreth, Yun Wei, Peiru Chen, Ke Zhang, Valeria Márquez-Pellegrin, Shanna Bonanno, Neel Joshi, Ming Guan, Mengdi Yang, Deng Li, Chiara Bellini, Fuguo Liu, Jianzhu Chen, Catherine J. Wu, David Barbie, Jiahe Li, Rizwan Romee

{"title":"Non-pathogenic E. coli displaying decoy-resistant IL18 mutein boosts anti-tumor and CAR NK cell responses","authors":"Shaobo Yang, Michal Sheffer, Isabel E. Kaplan, Zongqi Wang, Mubin Tarannum, Khanhlinh Dinh, Yasmin Abdulhamid, Eden Bobilev, Roman Shapiro, Rebecca Porter, Robert Soiffer, Jerome Ritz, John Koreth, Yun Wei, Peiru Chen, Ke Zhang, Valeria Márquez-Pellegrin, Shanna Bonanno, Neel Joshi, Ming Guan, Mengdi Yang, Deng Li, Chiara Bellini, Fuguo Liu, Jianzhu Chen, Catherine J. Wu, David Barbie, Jiahe Li, Rizwan Romee","doi":"10.1038/s41587-024-02418-6","DOIUrl":"https://doi.org/10.1038/s41587-024-02418-6","url":null,"abstract":"The tumor microenvironment can inhibit the efficacy of cancer therapies through mechanisms such as poor trafficking and exhaustion of immune cells. Here, to address this challenge, we exploited the safety, tumor tropism and ease of genetic manipulation of non-pathogenic Escherichia coli (E. coli) to deliver key immune-activating cytokines to tumors via surface display on the outer membrane of E. coli K-12 DH5α. Non-pathogenic E. coli expressing murine decoy-resistant IL18 mutein (DR18) induced robust CD8+ T and natural killer (NK) cell-dependent immune responses and suppressed tumor progression in immune-competent colorectal carcinoma and melanoma mouse models. E. coli K-12 DH5α engineered to display human DR18 potently activated mesothelin-targeting chimeric antigen receptor (CAR) NK cells and enhance their trafficking into tumors, which extended survival in an NK cell treatment-resistant mesothelioma xenograft model by enhancing TNF signaling and upregulating NK activation markers. Our live bacteria-based immunotherapeutic system safely and effectively induces potent anti-tumor responses in treatment-resistant solid tumors, motivating further evaluation of this approach in the clinic.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370003","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

TCR cell therapies vanquish solid tumors — finally TCR 细胞疗法终于战胜了实体瘤

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-10-02 DOI: 10.1038/s41587-024-02435-5

Charlotte Harrison

引用次数: 0

Rapid generation of long, chemically modified pegRNAs for prime editing 快速生成用于素材编辑的化学修饰长 pegRNA

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-30 DOI: 10.1038/s41587-024-02394-x

Xinlin Lei, Anhui Huang, Didi Chen, Xuebin Wang, Ruijin Ji, Jinlin Wang, Yizhou Zhang, Yuming Zhang, Shuhan Lu, Kun Zhang, Qiubing Chen, Ying Zhang, Hao Yin

{"title":"Rapid generation of long, chemically modified pegRNAs for prime editing","authors":"Xinlin Lei, Anhui Huang, Didi Chen, Xuebin Wang, Ruijin Ji, Jinlin Wang, Yizhou Zhang, Yuming Zhang, Shuhan Lu, Kun Zhang, Qiubing Chen, Ying Zhang, Hao Yin","doi":"10.1038/s41587-024-02394-x","DOIUrl":"https://doi.org/10.1038/s41587-024-02394-x","url":null,"abstract":"The editing efficiencies of prime editing (PE) using ribonucleoprotein (RNP) and RNA delivery are not optimal due to the challenges in solid-phase synthesis of long PE guide RNA (pegRNA) (>125 nt). Here, we develop an efficient, rapid and cost-effective method for generating chemically modified pegRNA (125–145 nt) and engineered pegRNA (epegRNA) (170–190 nt). We use an optimized splint ligation approach and achieve approximately 90% production efficiency for these RNAs, referred to as L-pegRNA and L-epegRNA. L-epegRNA demonstrates enhanced editing efficiencies across various cell lines and human primary cells with improvements of up to more than tenfold when using RNP delivery and several hundredfold with RNA delivery of PE, compared to epegRNA produced by in vitro transcription. L-epegRNA-mediated RNP delivery also outperforms plasmid-encoded PE in most comparisons. Our study provides a solution to obtaining high-quality pegRNA and epegRNA with desired chemical modifications, paving the way for the use of PE in therapeutics and various other fields.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329504","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