Nature Biomedical Engineering最新文献

Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases 与 Cas9 核酸酶相比，碱基编辑器和质点编辑器在 DNA 修复过程中发生 DNA 大缺失的频率低 20 倍

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-11-04 DOI: 10.1038/s41551-024-01277-5

Gue-Ho Hwang, Seok-Hoon Lee, Minsik Oh, Segi Kim, Omer Habib, Hyeon-Ki Jang, Heon Seok Kim, Youngkuk Kim, Chan Hyuk Kim, Sun Kim, Sangsu Bae

{"title":"Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases","authors":"Gue-Ho Hwang, Seok-Hoon Lee, Minsik Oh, Segi Kim, Omer Habib, Hyeon-Ki Jang, Heon Seok Kim, Youngkuk Kim, Chan Hyuk Kim, Sun Kim, Sangsu Bae","doi":"10.1038/s41551-024-01277-5","DOIUrl":"https://doi.org/10.1038/s41551-024-01277-5","url":null,"abstract":"When used to edit genomes, Cas9 nucleases produce targeted double-strand breaks in DNA. Subsequent DNA-repair pathways can induce large genomic deletions (larger than 100 bp), which constrains the applicability of genome editing. Here we show that Cas9-mediated double-strand breaks induce large deletions at varying frequencies in cancer cell lines, human embryonic stem cells and human primary T cells, and that most deletions are produced by two repair pathways: end resection and DNA-polymerase theta-mediated end joining. These findings required the optimization of long-range amplicon sequencing, the development of a k-mer alignment algorithm for the simultaneous analysis of large DNA deletions and small DNA alterations, and the use of CRISPR-interference screening. Despite leveraging mutated Cas9 nickases that produce single-strand breaks, base editors and prime editors also generated large deletions, yet at approximately 20-fold lower frequency than Cas9. We provide strategies for the mitigation of such deletions.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574622","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

Spatially resolved subcellular protein–protein interactomics in drug-perturbed lung-cancer cultures and tissues 药物干扰肺癌培养物和组织中空间分辨亚细胞蛋白质-蛋白质相互作用组学

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-30 DOI: 10.1038/s41551-024-01271-x

Shuangyi Cai, Thomas Hu, Abhijeet Venkataraman, Felix G. Rivera Moctezuma, Efe Ozturk, Nicholas Zhang, Mingshuang Wang, Tatenda Zvidzai, Sandip Das, Adithya Pillai, Frank Schneider, Suresh S. Ramalingam, You-Take Oh, Shi-Yong Sun, Ahmet F. Coskun

{"title":"Spatially resolved subcellular protein–protein interactomics in drug-perturbed lung-cancer cultures and tissues","authors":"Shuangyi Cai, Thomas Hu, Abhijeet Venkataraman, Felix G. Rivera Moctezuma, Efe Ozturk, Nicholas Zhang, Mingshuang Wang, Tatenda Zvidzai, Sandip Das, Adithya Pillai, Frank Schneider, Suresh S. Ramalingam, You-Take Oh, Shi-Yong Sun, Ahmet F. Coskun","doi":"10.1038/s41551-024-01271-x","DOIUrl":"https://doi.org/10.1038/s41551-024-01271-x","url":null,"abstract":"Protein–protein interactions (PPIs) regulate signalling pathways and cell phenotypes, and the visualization of spatially resolved dynamics of PPIs would thus shed light on the activation and crosstalk of signalling networks. Here we report a method that leverages a sequential proximity ligation assay for the multiplexed profiling of PPIs with up to 47 proteins involved in multisignalling crosstalk pathways. We applied the method, followed by conventional immunofluorescence, to cell cultures and tissues of non-small-cell lung cancers with a mutated epidermal growth-factor receptor to determine the co-localization of PPIs in subcellular volumes and to reconstruct changes in the subcellular distributions of PPIs in response to perturbations by the tyrosine kinase inhibitor osimertinib. We also show that a graph convolutional network encoding spatially resolved PPIs can accurately predict the cell-treatment status of single cells. Multiplexed proximity ligation assays aided by graph-based deep learning can provide insights into the subcellular organization of PPIs towards the design of drugs for targeting the protein interactome.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536903","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

Ultrabright and ultrafast afterglow imaging in vivo via nanoparticles made of trianthracene derivatives 通过三蒽衍生物制成的纳米颗粒进行超亮、超快的体内余辉成像

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-29 DOI: 10.1038/s41551-024-01274-8

Youjuan Wang, Jing Guo, Muchao Chen, Shiyi Liao, Li Xu, Qian Chen, Guosheng Song, Xiao-Bing Zhang

{"title":"Ultrabright and ultrafast afterglow imaging in vivo via nanoparticles made of trianthracene derivatives","authors":"Youjuan Wang, Jing Guo, Muchao Chen, Shiyi Liao, Li Xu, Qian Chen, Guosheng Song, Xiao-Bing Zhang","doi":"10.1038/s41551-024-01274-8","DOIUrl":"https://doi.org/10.1038/s41551-024-01274-8","url":null,"abstract":"Low sensitivity, photobleaching, high-power excitation and long acquisition times constrain the utility of afterglow luminescence. Here we report the design and imaging performance of nanoparticles made of electron-rich trianthracene derivatives that, on excitation by room light at ultralow power (58 μW cm–2), emit afterglow luminescence at ~500 times those of commonly used organic afterglow nanoparticles. The nanoparticles’ ultrabright afterglow allowed for deep-tissue imaging (up to 6 cm), for ultrafast afterglow imaging (at short acquisition times down to 0.01 s) of naturally behaving mice with negligible photobleaching, even after re-excitation for over 15 cycles, and for the accurate visualization of subcutaneous and orthotopic tumours and of plaque in carotid arteries. We also show that an afterglow nanoparticle that is activated only in the presence of granzyme B allowed for the tracking of granzyme-B activity in the context of therapeutic monitoring. The high sensitivity and negligible photobleaching of the organic afterglow nanoparticles offer advantages for real-time in vivo monitoring of physiopathological processes.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519963","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

Expanded toolkits for RNA circularization 用于 RNA 环化的扩展工具包

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-28 DOI: 10.1038/s41551-024-01262-y

Xiao Wang, Youkui Huang, Ling-Ling Chen

引用次数: 0

All-optical optoacoustics for clinical diagnostics 用于临床诊断的全光学光声技术

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-25 DOI: 10.1038/s41551-024-01270-y

X. Luís Deán-Ben

引用次数: 0

Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies 用于增强癌症疗法疗效的粘弹性合成抗原递呈细胞

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-25 DOI: 10.1038/s41551-024-01272-w

Zeyang Liu, Yan-Ruide Li, Youcheng Yang, Yu Zhu, Weihao Yuan, Tyler Hoffman, Yifan Wu, Enbo Zhu, Jana Zarubova, Jun Shen, Haochen Nan, Kun-Wei Yeh, Mohammad Mahdi Hasani-Sadrabadi, Yichen Zhu, Ying Fang, Xinyang Ge, Zhizhong Li, Jennifer Soto, Tzung Hsiai, Lili Yang, Song Li

{"title":"Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies","authors":"Zeyang Liu, Yan-Ruide Li, Youcheng Yang, Yu Zhu, Weihao Yuan, Tyler Hoffman, Yifan Wu, Enbo Zhu, Jana Zarubova, Jun Shen, Haochen Nan, Kun-Wei Yeh, Mohammad Mahdi Hasani-Sadrabadi, Yichen Zhu, Ying Fang, Xinyang Ge, Zhizhong Li, Jennifer Soto, Tzung Hsiai, Lili Yang, Song Li","doi":"10.1038/s41551-024-01272-w","DOIUrl":"https://doi.org/10.1038/s41551-024-01272-w","url":null,"abstract":"The use of synthetic antigen-presenting cells to activate and expand engineered T cells for the treatment of cancers typically results in therapies that are suboptimal in effectiveness and durability. Here we describe a high-throughput microfluidic system for the fabrication of synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells. Compared with rigid or elastic microspheres, the synthetic viscoelastic T-cell-activating cells (SynVACs) led to substantial enhancements in the expansion of human CD8+ T cells and to the suppression of the formation of regulatory T cells. Notably, activating and expanding chimaeric antigen receptor (CAR) T cells with SynVACs led to a CAR-transduction efficiency of approximately 90% and to substantial increases in T memory stem cells. The engineered CAR T cells eliminated tumour cells in a mouse model of human lymphoma, suppressed tumour growth in mice with human ovarian cancer xenografts, persisted for longer periods and reduced tumour-recurrence risk. Our findings underscore the crucial roles of viscoelasticity in T-cell engineering and highlight the utility of SynVACs in cancer therapy.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489208","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

Computational design of protein binders that boost the antitumour efficacy of CAR T cells 通过计算设计可提高 CAR T 细胞抗肿瘤功效的蛋白质结合剂

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-24 DOI: 10.1038/s41551-024-01263-x

引用次数: 0

Immunogenic amines on lipid nanoparticles 脂质纳米粒子上的免疫胺

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-23 DOI: 10.1038/s41551-024-01265-9

Preeti Sharma, Dor Breier, Dan Peer

引用次数: 0

Downregulating human leucocyte antigens on mesenchymal stromal cells by epigenetically repressing a β2-microglobulin super-enhancer 通过表观遗传抑制β2-微球蛋白超级增强子来下调间充质基质细胞上的人类白细胞抗原

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-21 DOI: 10.1038/s41551-024-01264-w

Fei Wang, Ran Li, Jing Yi Xu, Xiaoxia Bai, Ying Wang, Xu Ri Chen, Chen Pan, Shen Chen, Ke Zhou, Boon Chin Heng, Xuewei Wu, Wei Guo, Zhe Song, Shu Cheng Jin, Jing Zhou, Xiao Hui Zou, Hong Wei Ouyang, Hua Liu

{"title":"Downregulating human leucocyte antigens on mesenchymal stromal cells by epigenetically repressing a β2-microglobulin super-enhancer","authors":"Fei Wang, Ran Li, Jing Yi Xu, Xiaoxia Bai, Ying Wang, Xu Ri Chen, Chen Pan, Shen Chen, Ke Zhou, Boon Chin Heng, Xuewei Wu, Wei Guo, Zhe Song, Shu Cheng Jin, Jing Zhou, Xiao Hui Zou, Hong Wei Ouyang, Hua Liu","doi":"10.1038/s41551-024-01264-w","DOIUrl":"https://doi.org/10.1038/s41551-024-01264-w","url":null,"abstract":"Immune rejection caused by mismatches in human leucocyte antigens (HLAs) remains a major obstacle to the success of allogeneic cell therapies. Current strategies for the generation of ‘universal’ immune-compatible cells, particularly the editing of HLA class I (HLA-I) genes or the modulation of proteins that inhibit natural killer cells, often result in genomic instability or cellular cytotoxicity. Here we show that a β2-microglobulin super-enhancer (B2M-SE) that is responsive to interferon-γ is a critical regulator of the expression of HLA-I on mesenchymal stromal cells (MSCs). Targeted epigenetic repression of B2M-SE in MSCs reduced the surface expression of HLA-I below the threshold required to activate allogenic T cells while maintaining levels sufficient to evade cytotoxicity mediated by natural killer cells. In a humanized mouse model, the epigenetically edited MSCs demonstrated improved survival by evading the immune system, allowing them to exert enhanced therapeutic effects on LPS-induced acute lung injury. Targeted epigenetic repression of B2M-SE may facilitate the development of off-the-shelf cell sources for allogeneic cell therapy.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451816","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

Overcoming immune hurdles to implant longevity 克服免疫障碍，延长植入物寿命

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-10-17 DOI: 10.1038/s41551-024-01276-6

引用次数: 0