Hyun-Kee Min, Hongyu Zhao, Alexander Bahcheli, Peng Pan, Jade Chan, Junsheng Chen, Esther Low, Yuxiao Zhou, Xian Wang, Savo Bajic, Ran Peng, Siyi Wanggou, Qi Yang, Robert Du Yang Zhang, Leiming Wang, Xiufang Ren, Haoyue Qi, Yu Shi, Madeline N. Hayes, Brian Ciruna, Jüri Reimand, Xinyu Liu, Xi Huang
{"title":"Fluid shear stress activates a targetable mechano-metastatic cascade to promote medulloblastoma metastasis","authors":"Hyun-Kee Min, Hongyu Zhao, Alexander Bahcheli, Peng Pan, Jade Chan, Junsheng Chen, Esther Low, Yuxiao Zhou, Xian Wang, Savo Bajic, Ran Peng, Siyi Wanggou, Qi Yang, Robert Du Yang Zhang, Leiming Wang, Xiufang Ren, Haoyue Qi, Yu Shi, Madeline N. Hayes, Brian Ciruna, Jüri Reimand, Xinyu Liu, Xi Huang","doi":"10.1038/s41551-025-01487-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01487-5","url":null,"abstract":"<p>Biofluid flow generates fluid shear stress (FSS), a mechanical force widely present in the tissue microenvironment. How brain tumour growth alters the conduit of biofluid and impacts FSS-regulated cancer progression is unknown. Dissemination of medulloblastoma (MB) cells into the cerebrospinal fluid initiates metastasis within the central nervous system. Here, by simulating cerebrospinal fluid dynamics based on magnetic resonance imaging of patients with MB, we discover that FSS is elevated at the cervicomedullary junction. MB-relevant FSS promotes metastasis along the mouse spinal cord. Mechanistically, FSS induces metastatic cell behaviours, including weakened cell-substrate adhesion, increased motility, cell clustering and plasma membrane localization of glucose transporter 1 (GLUT1) to enhance glucose uptake. FSS is perceived by the mechanosensitive ion channel PIEZO2, which drives actomyosin contractility-dependent GLUT1 recruitment at the plasma membrane. Genetic targeting of PIEZO2 or pharmacologic inhibition of GLUT1 mitigates metastasis. Collectively, these findings define a targetable FSS-activated mechano-metastatic cascade for the treatment of MB metastasis.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"23 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927934","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":"A generalizable pathology foundation model using a unified knowledge distillation pretraining framework","authors":"Jiabo Ma, Zhengrui Guo, Fengtao Zhou, Yihui Wang, Yingxue Xu, Jinbang Li, Fang Yan, Yu Cai, Zhengjie Zhu, Cheng Jin, Yi Lin, Xinrui Jiang, Chenglong Zhao, Danyi Li, Anjia Han, Zhenhui Li, Ronald Cheong Kin Chan, Jiguang Wang, Peng Fei, Kwang-Ting Cheng, Shaoting Zhang, Li Liang, Hao Chen","doi":"10.1038/s41551-025-01488-4","DOIUrl":"https://doi.org/10.1038/s41551-025-01488-4","url":null,"abstract":"<p>The generalization ability of foundation models in the field of computational pathology (CPath) is crucial for their clinical success. However, current foundation models have only been evaluated on a limited type and number of tasks, leaving their generalization ability unclear. We establish a comprehensive benchmark to evaluate the performance of off-the-shelf foundation models across six distinct clinical task types, encompassing a total of 72 specific tasks. Our findings reveal that existing foundation models excel at certain task types but struggle to effectively handle the full breadth of clinical tasks. To improve the generalization of pathology foundation models, we propose a unified knowledge distillation framework consisting of both expert and self knowledge distillation, where the former allows the model to learn from the knowledge of multiple expert models, while the latter leverages self distillation to enable image representation learning via local–global alignment. On the basis of this framework, we develop a Generalizable Pathology Foundation Model (GPFM). Evaluated on the established benchmark, GPFM achieves an average rank of 1.6, ranking first in 42 tasks, positioning it as a promising method for feature representation in CPath.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"59 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927935","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 E. Woods, Fatima Alrashdan, Ellie C. Chen, Wendy Tan, Mathews John, Lukas Jaworski, Drew Bernard, Allison Post, Angel Moctezuma-Ramirez, Abdelmotagaly Elgalad, Alexander G. Steele, Sean M. Barber, Philip J. Horner, Amir H. Faraji, Dimitry G. Sayenko, Mehdi Razavi, Jacob T. Robinson
{"title":"Distributed battery-free bioelectronic implants with improved network power transfer efficiency via magnetoelectrics","authors":"Joshua E. Woods, Fatima Alrashdan, Ellie C. Chen, Wendy Tan, Mathews John, Lukas Jaworski, Drew Bernard, Allison Post, Angel Moctezuma-Ramirez, Abdelmotagaly Elgalad, Alexander G. Steele, Sean M. Barber, Philip J. Horner, Amir H. Faraji, Dimitry G. Sayenko, Mehdi Razavi, Jacob T. Robinson","doi":"10.1038/s41551-025-01489-3","DOIUrl":"https://doi.org/10.1038/s41551-025-01489-3","url":null,"abstract":"<p>Networks of miniature implants could enable simultaneous sensing and stimulation at different locations in the body, such as the heart and central or peripheral nervous system. This capability would support precise disease tracking and treatment or enable prosthetic technologies with many degrees of freedom. However, wireless power and data transfer are often inefficient through biological tissues, particularly as the number of implanted devices increases. Here we show that magnetoelectric wireless data and power transfer supports a network of millimetre-sized bioelectronic implants in which system efficiency improves with additional devices. We demonstrate wireless, battery-free networks ranging from one to six implants, where the total system efficiency increases from 0.2% to 1.3%, with each node receiving 2.2 mW at 1 cm distance. We show proof-of-concept networks of miniature spinal cord stimulators and cardiac pacing devices in large animals via efficient and robust wireless power transfer. These magnetoelectric implants provide a scalable network architecture of bioelectronic implants for next-generation electronic medicine.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"13 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910712","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}
Zhenhao Fang, Valter S. Monteiro, Changin Oh, Kawthar Al Janabi, Luciano Romero, Nabihah Ahsan, Luojia Yang, Lei Peng, Daniel DiMaio, Carolina Lucas, Sidi Chen
{"title":"A modular vaccine platform for optimized lipid nanoparticle mRNA immunogenicity","authors":"Zhenhao Fang, Valter S. Monteiro, Changin Oh, Kawthar Al Janabi, Luciano Romero, Nabihah Ahsan, Luojia Yang, Lei Peng, Daniel DiMaio, Carolina Lucas, Sidi Chen","doi":"10.1038/s41551-025-01478-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01478-6","url":null,"abstract":"<p>Certain messenger RNA antigens in mRNA vaccines elicit an insufficient immune response due to challenges in cell surface translocation (CST) of the antigens. Here we develop a modular vaccine platform (MVP) to enhance the immunogenicity of challenging mRNA antigens by optimizing antigen expression and presentation. MVPs enable the modular assembly of chimeric antigens. Our platform comprises diverse modules capable of generating >2,500 combinations with any antigen and displaying distinct antigen epitopes on the cell surface. We quantify the CST efficacy of various modules using multiple antigens, including the mpox virus (MPXV) proteins A29, M1R and A35R, and compare chimeric antigen surface expression in multiple cell lines. Using MPXV as a model, we identify optimal modules that enhance the CST of multiple MPXV antigens, improving the immune response of lipid nanoparticle mRNAs and protecting against lethal viral challenge. With these effective CST modules, we further demonstrate the generalizability of MVP by optimizing additional mRNA antigens, including the human papillomavirus 16 proteins E6 and E7 and the varicella zoster virus glycoprotein gE. This platform is applicable to any antigen of interest, facilitating the development of mRNA vaccines against challenging targets.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"110 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900377","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}
Mark Buckup, Igor Figueiredo, Giorgio Ioannou, Sinem Ozbey, Rafael Cabal, Alexandra Tabachnikova, Leanna Troncoso, Jessica Le Berichel, Zhen Zhao, Stephen C. Ward, Clotilde Hennequin, Guray Akturk, Steve Hamel, Maria Isabel Fiel, Rachel Brody, Myron Schwartz, Thomas U. Marron, Seunghee Kim-Schulze, Vladimir Roudko, Edgar Gonzalez-Kozlova, Pauline Hamon, Miriam Merad, Sacha Gnjatic
{"title":"Multiparametric cellular and spatial organization in cancer tissue lesions with a streamlined pipeline","authors":"Mark Buckup, Igor Figueiredo, Giorgio Ioannou, Sinem Ozbey, Rafael Cabal, Alexandra Tabachnikova, Leanna Troncoso, Jessica Le Berichel, Zhen Zhao, Stephen C. Ward, Clotilde Hennequin, Guray Akturk, Steve Hamel, Maria Isabel Fiel, Rachel Brody, Myron Schwartz, Thomas U. Marron, Seunghee Kim-Schulze, Vladimir Roudko, Edgar Gonzalez-Kozlova, Pauline Hamon, Miriam Merad, Sacha Gnjatic","doi":"10.1038/s41551-025-01475-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01475-9","url":null,"abstract":"<p>Multiplex immunostaining analysis remains fragmented, underperforming and labour intensive despite tissue proteomic methodologies achieving ever-increasing marker complexity. Here we propose an open-source, user-guided automated pipeline that streamlines start-to-finish, single-cell resolution analysis of whole-slide tissue, named multiplex-imaging analysis, registration, quantification and overlaying (MARQO). MARQO integrates elastic image registration, iterative nuclear segmentation, unsupervised clustering with mini-batch <i>k</i>-means and user-guided cell classification through a graphical interface. We compare and validate MARQO using multiplexed immunohistochemical consecutive staining on a single slide using human tumour and adjacent normal tissue samples. Performance is compared with manually curated pathologist determinations and quantification of multiple markers. We optimize MARQO to analyse diverse tissue sizes from whole tissue, biopsy, and tissue microarray and staining approaches, such as singleplex immunohistochemistry and 20-colour multiplex immunofluorescence, to determine marker co-expression patterns in multiple human solid cancer types. Lastly, we validate CD8<sup>+</sup> T cell enrichment in hepatocellular carcinoma responders to neoadjuvant cemiplimab in a phase 2 clinical trial, further showing the ability of MARQO to identify spatially resolved in situ mechanisms by providing multiplex whole-slide single-cell resolution data.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"82 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900376","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}
Tomasz M. Grzywa, Alexandra Neeser, Ranjani Ramasubramanian, Anna Romanov, Ryan Tannir, Naveen K. Mehta, Benjamin Cossette, Duncan M. Morgan, Beatriz Goncalves, Ina Sukaj, Elisa Bergaggio, Stephan Kadauke, Regina M. Myers, Luca Paruzzo, Guido Ghilardi, Austin Cozzone, Stephen J. Schuster, Noelle Frey, Libin Zhang, Parisa Yousefpour, Wuhbet Abraham, Heikyung Suh, Marco Ruella, Stephan A. Grupp, Roberto Chiarle, K. Dane Wittrup, Leyuan Ma, Darrell J. Irvine
{"title":"Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells","authors":"Tomasz M. Grzywa, Alexandra Neeser, Ranjani Ramasubramanian, Anna Romanov, Ryan Tannir, Naveen K. Mehta, Benjamin Cossette, Duncan M. Morgan, Beatriz Goncalves, Ina Sukaj, Elisa Bergaggio, Stephan Kadauke, Regina M. Myers, Luca Paruzzo, Guido Ghilardi, Austin Cozzone, Stephen J. Schuster, Noelle Frey, Libin Zhang, Parisa Yousefpour, Wuhbet Abraham, Heikyung Suh, Marco Ruella, Stephan A. Grupp, Roberto Chiarle, K. Dane Wittrup, Leyuan Ma, Darrell J. Irvine","doi":"10.1038/s41551-025-01470-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01470-0","url":null,"abstract":"<p>Chimeric antigen receptor (CAR) T cell therapy targeting CD19 elicits remarkable clinical efficacy in B cell malignancies, but many patients relapse owing to failed expansion and/or progressive loss of CAR-T cells. We recently reported a strategy to potently restimulate CAR-T cells in vivo, enhancing their functionality by administration of a vaccine-like stimulus comprised of surrogate peptide ligands for a CAR linked to a lymph node-targeting amphiphilic PEG-lipid (amph-vax). Here we demonstrate a general strategy to discover and optimize peptide mimotopes enabling amph-vax generation for any CAR. We use yeast surface display to identify peptide binders to FMC63 (the scFv used in clinical CD19 CARs), which are then subsequently affinity matured by directed evolution. CAR-T vaccines using these optimized mimotopes triggered marked expansion and memory development of CD19 CAR-T cells in both syngeneic and humanized mouse models of B-acute lymphoblastic leukaemia/lymphoma, and enhanced control of disease progression compared with CD19 CAR-T-only-treated mice. This approach enables amph-vax boosting to be applied to any clinically relevant CAR-T cell product.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"13 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900375","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":"Towards a multi-organ, multi-omics medical digital twin","authors":"Junhao Wen","doi":"10.1038/s41551-025-01474-w","DOIUrl":"10.1038/s41551-025-01474-w","url":null,"abstract":"Medical digital twins hold promises for advancing personalized medicine. With the rapid growth of multi-organ and multi-omics biomedical data, artificial intelligence can drive more holistic and integrated medical digital twins for human ageing and disease.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 9","pages":"1386-1389"},"PeriodicalIF":26.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900374","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}
Zakary S. Singer, Jonathan Pabón, Hsinyen Huang, William Sun, Hongsheng Luo, Kailyn Rhyah Grant, Ijeoma Obi, Courtney Coker, Charles M. Rice, Tal Danino
{"title":"Engineered bacteria launch and control an oncolytic virus","authors":"Zakary S. Singer, Jonathan Pabón, Hsinyen Huang, William Sun, Hongsheng Luo, Kailyn Rhyah Grant, Ijeoma Obi, Courtney Coker, Charles M. Rice, Tal Danino","doi":"10.1038/s41551-025-01476-8","DOIUrl":"https://doi.org/10.1038/s41551-025-01476-8","url":null,"abstract":"<p>The ability of bacteria and viruses to selectively replicate in tumours has led to synthetic engineering of new microbial therapies. Here we design a cooperative strategy whereby <i>Salmonella typhimurium</i> bacteria transcribe and deliver the Senecavirus A RNA genome inside host cells, launching a potent oncolytic viral infection. ‘Encapsidated’ by bacteria, the viral genome can further bypass circulating antiviral antibodies to reach the tumour and initiate replication and spread within immune mice. Finally, we engineer the virus to require a bacterially delivered protease to achieve virion maturation, demonstrating bacterial control over the virus. Together, we refer to this platform as ‘CAPPSID’ for Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery. This work extends bacterially delivered therapeutics to viral genomes, and shows how a consortium of microbes can achieve a cooperative aim.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"177 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851406","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}
Miao Yu, Limei Ai, Bang Wang, Shifeng Lian, Lawrence Ip, James Liu, Linxian Li, Shengdar Q. Tsai, Benjamin P. Kleinstiver, Zongli Zheng
{"title":"GenomePAM directs PAM characterization and engineering of CRISPR-Cas nucleases using mammalian genome repeats","authors":"Miao Yu, Limei Ai, Bang Wang, Shifeng Lian, Lawrence Ip, James Liu, Linxian Li, Shengdar Q. Tsai, Benjamin P. Kleinstiver, Zongli Zheng","doi":"10.1038/s41551-025-01464-y","DOIUrl":"https://doi.org/10.1038/s41551-025-01464-y","url":null,"abstract":"<p>Characterizing the protospacer adjacent motif (PAM) requirements of different Cas enzymes is a bottleneck in the discovery of Cas proteins and their engineered variants in mammalian cell contexts. Here, to overcome this challenge and to enable more scalable characterization of PAM preferences, we develop a method named GenomePAM that allows for direct PAM characterization in mammalian cells. GenomePAM leverages genomic repetitive sequences as target sites and does not require protein purification or synthetic oligos. GenomePAM uses a 20-nt protospacer that occurs ~16,942 times in every human diploid cell and is flanked by nearly random sequences. We demonstrate that GenomePAM can accurately characterize the PAM requirement of type II and type V nucleases, including the minimal PAM requirement of the near-PAMless SpRY and extended PAM for CjCas9. Beyond PAM characterization, GenomePAM allows for simultaneous comparison of activities and fidelities among different Cas nucleases on thousands of match and mismatch sites across the genome using a single gRNA and provides insight into the genome-wide chromatin accessibility profiles in different cell types.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"26 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825294","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}
Saijuan Xu, Dan Liang, Qiudao Wang, Yan Cheng, Da Xie, Yang Gui, Haokun Zhang, Changrui Feng, Feiyan Zhao, Wendan Ren, Gongrui Sun, Yang Yang, Lin Li, Yongrong Lai, Bin Fu, Yuming Lu, Zi Jun Wang, Yuxuan Wu
{"title":"In vivo genome editing of human haematopoietic stem cells for treatment of blood disorders using mRNA delivery","authors":"Saijuan Xu, Dan Liang, Qiudao Wang, Yan Cheng, Da Xie, Yang Gui, Haokun Zhang, Changrui Feng, Feiyan Zhao, Wendan Ren, Gongrui Sun, Yang Yang, Lin Li, Yongrong Lai, Bin Fu, Yuming Lu, Zi Jun Wang, Yuxuan Wu","doi":"10.1038/s41551-025-01480-y","DOIUrl":"https://doi.org/10.1038/s41551-025-01480-y","url":null,"abstract":"<p>Ex vivo autologous haematopoietic stem cell (HSC) gene therapy provides a promising treatment option for haematological disorders. However, current methods involve complex processes and chemotherapeutic conditioning, leading to limited accessibility for treatment and major side effects. Here we develop antibody-free targeted lipid nanoparticles (LNPs) for mRNA delivery to HSCs in vivo, enabling efficient base editing of the γ-globin gene (<i>HBG1/2</i>) promoter target in human HSCs to reactivate fetal haemoglobin in derived erythroid cells. Delivery of ABE8e/sgRNA mRNA with optimized LNPs achieves efficient in vivo base editing of <i>HBG1/2</i> in transfusion-dependent β-thalassaemia (TDT) patient-derived HSCs engrafted in immunodeficient NCG-X mice, showing restored globin chain balance in erythroid cells. Our research indicates that using LNPs for genome editor delivery achieves efficient editing of endogenous genes of human HSCs. This non-viral delivery system eliminates the need for collecting or mobilizing HSCs, providing a potent and one-time treatment potential for blood disorders such as sickle cell disease and TDT.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"27 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819140","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}
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