{"title":"Setting morphogen gradients","authors":"Valeria Caprettini","doi":"10.1038/s41551-024-01295-3","DOIUrl":"10.1038/s41551-024-01295-3","url":null,"abstract":"DNA microbeads loaded with an agonist for Wnt and injected into retinal organoids allow for the spatiotemporal control of gradients of the morphogen to better direct organoid development and maturation.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 11","pages":"1329-1329"},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637029","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}
Joshua C. Chen, Abdeali Dhuliyawalla, Robert Garcia, Ariadna Robledo, Joshua E. Woods, Fatima Alrashdan, Sean O’Leary, Adam Husain, Anthony Price, Scott Crosby, Michelle M. Felicella, Ajay K. Wakhloo, Patrick Karas, Nicole Provenza, Wayne Goodman, Sameer A. Sheth, Sunil A. Sheth, Jacob T. Robinson, Peter Kan
{"title":"Endocisternal interfaces for minimally invasive neural stimulation and recording of the brain and spinal cord","authors":"Joshua C. Chen, Abdeali Dhuliyawalla, Robert Garcia, Ariadna Robledo, Joshua E. Woods, Fatima Alrashdan, Sean O’Leary, Adam Husain, Anthony Price, Scott Crosby, Michelle M. Felicella, Ajay K. Wakhloo, Patrick Karas, Nicole Provenza, Wayne Goodman, Sameer A. Sheth, Sunil A. Sheth, Jacob T. Robinson, Peter Kan","doi":"10.1038/s41551-024-01281-9","DOIUrl":"https://doi.org/10.1038/s41551-024-01281-9","url":null,"abstract":"<p>Minimally invasive neural interfaces can be used to diagnose, manage and treat many disorders, with reduced risks of surgical complications. However, endovascular probes lack access to key cortical, subcortical and spinal targets, and are not typically explantable after endothelialization. Here we report the development and testing, in sheep, of endocisternal neural interfaces that approach brain and spinal cord targets through inner and outer spaces filled with cerebrospinal fluid. Thus, the interfaces gain access to the entire brain convexity, to deep brain structures within the ventricles and to the spinal cord from the spinal subarachnoid space. We combined an endocisternal neural interface with wireless miniature magnetoelectrically powered bioelectronics so that it can be freely navigated percutaneously from the spinal space to the cranial subarachnoid space, and from the cranial subarachnoid space to the ventricles. In sheep, we show recording and stimulation functions, as well as repositioning of the flexible electrodes and explantation of the interface after chronic implantation. Minimally invasive endocisternal bioelectronics may enable chronic and transient therapies, particularly for stroke rehabilitation and epilepsy monitoring.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"245 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598338","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}
Saehyuck Oh, Janghwan Jekal, Jinyoung Won, Kyung Seob Lim, Chang-Yeop Jeon, Junghyung Park, Hyeon-Gu Yeo, Yu Gyeong Kim, Young Hee Lee, Leslie Jaesun Ha, Han Hee Jung, Junwoo Yea, Hyeokjun Lee, Jeongdae Ha, Jinmo Kim, Doyoung Lee, Soojeong Song, Jieun Son, Tae Sang Yu, Jungmin Lee, Sanghoon Lee, Jaehong Lee, Bong Hoon Kim, Ji-Woong Choi, Jong-Cheol Rah, Young Min Song, Jae-Woong Jeong, Hyung Jin Choi, Sheng Xu, Youngjeon Lee, Kyung-In Jang
{"title":"A stealthy neural recorder for the study of behaviour in primates","authors":"Saehyuck Oh, Janghwan Jekal, Jinyoung Won, Kyung Seob Lim, Chang-Yeop Jeon, Junghyung Park, Hyeon-Gu Yeo, Yu Gyeong Kim, Young Hee Lee, Leslie Jaesun Ha, Han Hee Jung, Junwoo Yea, Hyeokjun Lee, Jeongdae Ha, Jinmo Kim, Doyoung Lee, Soojeong Song, Jieun Son, Tae Sang Yu, Jungmin Lee, Sanghoon Lee, Jaehong Lee, Bong Hoon Kim, Ji-Woong Choi, Jong-Cheol Rah, Young Min Song, Jae-Woong Jeong, Hyung Jin Choi, Sheng Xu, Youngjeon Lee, Kyung-In Jang","doi":"10.1038/s41551-024-01280-w","DOIUrl":"https://doi.org/10.1038/s41551-024-01280-w","url":null,"abstract":"<p>By monitoring brain neural signals, neural recorders allow for the study of neurological mechanisms underlying specific behavioural and cognitive states. However, the large brain volumes of non-human primates and their extensive range of uncontrolled movements and inherent wildness make it difficult to carry out covert and long-term recording and analysis of deep-brain neural signals. Here we report the development and performance of a stealthy neural recorder for the study of naturalistic behaviours in non-human primates. The neural recorder includes a fully implantable wireless and battery-free module for the recording of local field potentials and accelerometry data in real time, a flexible 32-electrode neural probe with a resorbable insertion shuttle, and a repeater coil-based wireless-power-transfer system operating at the body scale. We used the device to record neurobehavioural data for over 1 month in a freely moving monkey and leveraged the recorded data to train an artificial intelligence model for the classification of the animals’ eating behaviours.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"95 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597609","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}
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":"<p>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 <i>k</i>-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.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"68 1","pages":""},"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}
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":"<p>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.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"11 1","pages":""},"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}
{"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":"<p>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<sup>–2</sup>), 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.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"71 1","pages":""},"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}
{"title":"Expanded toolkits for RNA circularization","authors":"Xiao Wang, Youkui Huang, Ling-Ling Chen","doi":"10.1038/s41551-024-01262-y","DOIUrl":"https://doi.org/10.1038/s41551-024-01262-y","url":null,"abstract":"Optimized methods for the synthesis of circular RNA in vitro and in cells, and a complementary Cas9 de-immunization method, enhance RNA persistence and reduce immunogenicity for applications in genome engineering and cell engineering.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"23 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519259","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}
{"title":"All-optical optoacoustics for clinical diagnostics","authors":"X. Luís Deán-Ben","doi":"10.1038/s41551-024-01270-y","DOIUrl":"https://doi.org/10.1038/s41551-024-01270-y","url":null,"abstract":"The quality of three-dimensional optoacoustic images of subcutaneous microvasculature in patients can be enhanced by reducing the scan times of all-optical Fabry–Pérot scanners to a few seconds.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"1 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489207","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}
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":"<p>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<sup>+</sup> 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.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 1","pages":""},"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}
{"title":"Computational design of protein binders that boost the antitumour efficacy of CAR T cells","authors":"","doi":"10.1038/s41551-024-01263-x","DOIUrl":"https://doi.org/10.1038/s41551-024-01263-x","url":null,"abstract":"We computationally designed protein binders for chimeric antigen receptor (CAR) constructs to target the glioblastoma-associated antigens EGFR and CD276. Compared with standard CAR T cells, CAR T cells with the de novo-designed binders showed enhanced proliferation, cytokine release and resistance to exhaustion, as well as superior antitumour effects in vitro and in vivo.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"4 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488424","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}