{"title":"Brazil’s low-cost CAR-Ts take on Global South","authors":"","doi":"10.1038/s41587-025-02691-z","DOIUrl":"https://doi.org/10.1038/s41587-025-02691-z","url":null,"abstract":"<p>Brazil is the first country in Latin America to produce its own cut-price chimeric antigen receptor (CAR)-T cell therapies. Now, Caring Cross, a US-based non-profit focused on making advanced therapies affordable, plans to expands Brazil’s model to Turkey and the Middle East.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"132 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066966","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}
{"title":"A gut-derived peptide protects citrus trees from Huanglongbing","authors":"Iris Marchal","doi":"10.1038/s41587-025-02687-9","DOIUrl":"https://doi.org/10.1038/s41587-025-02687-9","url":null,"abstract":"<p>Huanglongbing is a devastating bacterial disease of citrus trees with no known cure. An emerging strategy to provide resistance to plant pathogens is disrupting genes that increase disease susceptibility. A paper in <i>Science</i> by Zhao et al. uses this approach in citrus trees, and identifies a regulatory circuit that can be modulated to alleviate Huanglongbing disease symptoms.</p><p>Huanglongbing can infect all citrus plants, and only some lineages naturally display tolerance or resistance. This prompted the authors to compare the transcriptional responses of different lineages upon infection. They found the E3 ubiquitin ligase <i>PUB21</i> to be highly upregulated in disease-sensitive plants, but not in disease-tolerant plants. Further analysis showed that PUB21 targets MYC2 — an immune protein that is important for jasmonate-mediated defense — for degradation. PUB21 and MYC2 form a regulatory circuit, in which MYC2 binds the <i>PUB21</i> promotor to induce PUB21 expression, thereby degrading MYC2. The authors found that the Huanglongbing pathogen targets this circuit by enhancing the PUB21–MYC2 interaction to suppress immune defense and promote infection.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"29 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067049","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}
{"title":"3D bioprinting innovation and the patentability hurdle","authors":"Pratap Devarapalli, Dianne Nicol, Jane Nielsen","doi":"10.1038/s41587-025-02661-5","DOIUrl":"https://doi.org/10.1038/s41587-025-02661-5","url":null,"abstract":"How are patent examiners in the United States, Europe and Australia interpreting and applying the patentability criteria to specific subject matter related to 3D bioprinting technologies?","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"1 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066969","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}
Feyisayo Eweje, Vanessa Ibrahim, Aram Shajii, Michelle L. Walsh, Kiran Ahmad, Assma Alrefai, Dominie Miyasato, Jessie R. Davis, Hyunok Ham, Kaicheng Li, Michael Roehrl, Carolyn A. Haller, David R. Liu, Jiaxuan Chen, Elliot L. Chaikof
{"title":"Self-assembling protein nanoparticles for cytosolic delivery of nucleic acids and proteins","authors":"Feyisayo Eweje, Vanessa Ibrahim, Aram Shajii, Michelle L. Walsh, Kiran Ahmad, Assma Alrefai, Dominie Miyasato, Jessie R. Davis, Hyunok Ham, Kaicheng Li, Michael Roehrl, Carolyn A. Haller, David R. Liu, Jiaxuan Chen, Elliot L. Chaikof","doi":"10.1038/s41587-025-02664-2","DOIUrl":"https://doi.org/10.1038/s41587-025-02664-2","url":null,"abstract":"<p>Intracellular delivery of biomacromolecules is hampered by low efficiency and cytotoxicity. Here we report the development of elastin-based nanoparticles for therapeutic delivery (ENTER), a recombinant elastin-like polypeptide (ELP)-based delivery system for effective cytosolic delivery of biomacromolecules in vitro and in vivo. Through iterative design, we developed fourth-generation ELPs fused to cationic endosomal escape peptides (EEPs) that self-assemble into pH-responsive micellar nanoparticles and enable cytosolic entry of cargo following endocytic uptake. In silico screening of α-helical peptide libraries led to the discovery of an EEP (EEP13) with 48% improved protein delivery efficiency versus a benchmark peptide. Our lead ELP–EEP13 showed similar or superior performance compared to lipid-based transfection reagents in the delivery of mRNA-encoded, DNA-encoded and protein-form Cre recombinase and CRISPR gene editors as well as short interfering RNAs to multiple cell lines and primary cell types. Intranasal administration of ELP–EEP13 combined with Cre protein achieved efficient editing of lung epithelial cells in reporter mice.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"125 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979368","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}
Pei Su, Michael A. R. Hollas, Indira Pla, Stanislav Rubakhin, Fatma Ayaloglu Butun, Joseph B. Greer, Bryan P. Early, Ryan T. Fellers, Michael A. Caldwell, Jonathan V. Sweedler, Jared O. Kafader, Neil L. Kelleher
{"title":"Proteoform profiling of endogenous single cells from rat hippocampus at scale","authors":"Pei Su, Michael A. R. Hollas, Indira Pla, Stanislav Rubakhin, Fatma Ayaloglu Butun, Joseph B. Greer, Bryan P. Early, Ryan T. Fellers, Michael A. Caldwell, Jonathan V. Sweedler, Jared O. Kafader, Neil L. Kelleher","doi":"10.1038/s41587-025-02669-x","DOIUrl":"https://doi.org/10.1038/s41587-025-02669-x","url":null,"abstract":"<p>We perform intact proteoform profiling of 10,809 endogenous single cells from the rat hippocampus using single-cell proteoform imaging mass spectrometry (scPiMS). scPiMS directly extracts whole proteins and demonstrates high throughput for MS-based single-cell proteomics compared with existing approaches. We develop an informatics workflow dedicated to this datatype and use it to assign neurons, astrocytes or microglia cell types according to their proteoform signatures.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"12 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979370","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}
{"title":"Targeting a cell surface RNA-binding protein driving acute myeloid leukemia","authors":"","doi":"10.1038/s41587-025-02695-9","DOIUrl":"https://doi.org/10.1038/s41587-025-02695-9","url":null,"abstract":"How modifications to RNA molecules and the proteins they interact with on the cell surface contribute to cancer is largely unknown. Preclinical evidence indicates that cell surface nucleophosmin (NPM1, an RNA-binding protein) is a novel druggable biomarker in acute myeloid leukemia, with potential implications for improving detection and immunotherapy strategies for several cancer types.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"240 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933283","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}
Lei Chang, Yang Xie, Brett Taylor, Zhaoning Wang, Jiachen Sun, Ethan J. Armand, Shreya Mishra, Jie Xu, Melodi Tastemel, Audrey Lie, Zane A. Gibbs, Hannah S. Indralingam, Tuyet M. Tan, Rafael Bejar, Clark C. Chen, Frank B. Furnari, Ming Hu, Bing Ren
{"title":"Author Correction: Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues","authors":"Lei Chang, Yang Xie, Brett Taylor, Zhaoning Wang, Jiachen Sun, Ethan J. Armand, Shreya Mishra, Jie Xu, Melodi Tastemel, Audrey Lie, Zane A. Gibbs, Hannah S. Indralingam, Tuyet M. Tan, Rafael Bejar, Clark C. Chen, Frank B. Furnari, Ming Hu, Bing Ren","doi":"10.1038/s41587-025-02697-7","DOIUrl":"https://doi.org/10.1038/s41587-025-02697-7","url":null,"abstract":"<p>Correction to: <i>Nature Biotechnology</i> https://doi.org/10.1038/s41587-024-02447-1, published online 18 October 2024.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"44 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933277","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}
{"title":"A protein association atlas for human tissues","authors":"","doi":"10.1038/s41587-025-02692-y","DOIUrl":"https://doi.org/10.1038/s41587-025-02692-y","url":null,"abstract":"Proteomics samples of human cancer biopsies were combined to derive an atlas of protein–protein associations for human tissues. Differences between tissues are not strongly driven by gene expression but could, in part, be due to tissue-specific subcellular components and processes.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"3 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933278","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}
Soumya Kannan, Han Altae-Tran, Shiyou Zhu, Peiyu Xu, Daniel Strebinger, Rachel Oshiro, Guilhem Faure, Lukas Moeller, Julie Pham, Kepler S. Mears, Heyuan M. Ni, Rhiannon K. Macrae, Feng Zhang
{"title":"Evolution-guided protein design of IscB for persistent epigenome editing in vivo","authors":"Soumya Kannan, Han Altae-Tran, Shiyou Zhu, Peiyu Xu, Daniel Strebinger, Rachel Oshiro, Guilhem Faure, Lukas Moeller, Julie Pham, Kepler S. Mears, Heyuan M. Ni, Rhiannon K. Macrae, Feng Zhang","doi":"10.1038/s41587-025-02655-3","DOIUrl":"https://doi.org/10.1038/s41587-025-02655-3","url":null,"abstract":"<p>Naturally existing enzymes have been adapted for a variety of molecular technologies, with enhancements or modifications to the enzymes introduced to improve the desired function; however, it is difficult to engineer variants with enhanced activity while maintaining specificity. Here we engineer the compact Obligate Mobile Element Guided Activity (OMEGA) RNA-guided endonuclease IscB and its guiding RNA (ωRNA) by combining ortholog screening, structure-guided protein domain design and RNA engineering, and deep learning-based structure prediction to generate an improved variant, NovaIscB. We show that the compact NovaIscB achieves up to 40% indel activity (~100-fold improvement over wild-type OgeuIscB) on the human genome with improved specificity relative to existing IscBs. We further show that NovaIscB can be fused with a methyltransferase to create a programmable transcriptional repressor, OMEGAoff, that is compact enough to be packaged in a single adeno-associated virus vector for persistent in vivo gene repression. This study highlights the power of combining natural diversity with protein engineering to design enhanced enzymes for molecular biology applications.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"116 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915841","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}
Roger A. Barker, Nicholas P. Lao-Kaim, Natalie Valle Guzman, Dilan Athauda, Hjalmar Bjartmarz, Anders Björklund, Alistair Church, Emma Cutting, Danielle Daft, Viswas Dayal, Stephen Dunnett, Amy Evans, Shane Grealish, Naomi Hannaway, Xiaoling He, Sam Hewitt, Zinovia Kefalopoulou, Philipp Mahlknecht, Antonio Martín-Bastida, Krista Farrell, Sarah Moore, Harry Bulstrode, Tagore Nakornchai, Jenny Nelander-Wahlestedt, Linnea Roupé, Gesine Paul, Kathryn Peall, Anne Rosser, Adriana Roca-Fernández, Sophie Rowlands, Anne-Marie McGorrian, Caroline Scherf, Ngoc Nga Vinh, Victoria Roberton, Claire Kelly, Mariah Lelos, Eduardo Torres, Kate Shires, Rachel Hills, Debbie Williams, Andreas-Antonios Roussakis, Krista Sibley, Pamela Tyers, Ruwani Wijeyekoon, Caroline Williams-Gray, Thomas Foltynie, Paola Piccini, Robert Morris, Stanley E. Lazic, Olle Lindvall, Malin Parmar, Hakan Widner
{"title":"The TransEuro open-label trial of human fetal ventral mesencephalic transplantation in patients with moderate Parkinson’s disease","authors":"Roger A. Barker, Nicholas P. Lao-Kaim, Natalie Valle Guzman, Dilan Athauda, Hjalmar Bjartmarz, Anders Björklund, Alistair Church, Emma Cutting, Danielle Daft, Viswas Dayal, Stephen Dunnett, Amy Evans, Shane Grealish, Naomi Hannaway, Xiaoling He, Sam Hewitt, Zinovia Kefalopoulou, Philipp Mahlknecht, Antonio Martín-Bastida, Krista Farrell, Sarah Moore, Harry Bulstrode, Tagore Nakornchai, Jenny Nelander-Wahlestedt, Linnea Roupé, Gesine Paul, Kathryn Peall, Anne Rosser, Adriana Roca-Fernández, Sophie Rowlands, Anne-Marie McGorrian, Caroline Scherf, Ngoc Nga Vinh, Victoria Roberton, Claire Kelly, Mariah Lelos, Eduardo Torres, Kate Shires, Rachel Hills, Debbie Williams, Andreas-Antonios Roussakis, Krista Sibley, Pamela Tyers, Ruwani Wijeyekoon, Caroline Williams-Gray, Thomas Foltynie, Paola Piccini, Robert Morris, Stanley E. Lazic, Olle Lindvall, Malin Parmar, Hakan Widner","doi":"10.1038/s41587-025-02567-2","DOIUrl":"https://doi.org/10.1038/s41587-025-02567-2","url":null,"abstract":"<p>Transplantation of human fetal ventral mesencephalic tissue in individuals with Parkinson’s disease has yielded clinical benefits but also side effects, such as graft-induced dyskinesias. The open-label TransEuro trial (NCT01898390) was designed to determine whether this approach could be further developed into a clinically useful treatment. Owing to poor availability of human fetal ventral mesencephalic tissue, only 11 individuals were grafted at two centers using the same tissue preparation protocol but different implantation devices. No overall clinical effect was seen for the primary endpoint 3 years after grafting. No major graft-induced dyskinesias were seen, but we observed differences in outcome related to transplant device and/or site. Mean dopamine uptake improved at 18 months in seven individuals according to [<sup>18</sup>F]fluorodopa positron emission tomography imaging but was restored to near-normal levels in only one individual. Our findings highlight the need for a stem cell source of dopamine neurons for potential Parkinson’s disease cell therapy and provide critical insights into how such clinical studies should be approached.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"138 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898170","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}
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