{"title":"Amyloid is everywhere, but new treatments could stop the toxic build up","authors":"Cormac Sheridan","doi":"10.1038/s41587-024-02471-1","DOIUrl":"10.1038/s41587-024-02471-1","url":null,"abstract":"Amyloid deposits are present in the brains of cognitively impaired individuals, but also accumulate throughout the body. Some biotechs aim to keep these misfolded proteins in check to treat a range of diseases, including heart failure, ALS and Alzheimer’s disease.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1625-1628"},"PeriodicalIF":33.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02471-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Italy tests first gene-edited vines for winemaking","authors":"Anna Meldolesi","doi":"10.1038/s41587-024-02478-8","DOIUrl":"10.1038/s41587-024-02478-8","url":null,"abstract":"Europe’s first field trial of gene-edited vines began in northern Italy on 30 September 2024. Developed by EdiVite, a spinoff from the University of Verona, these Chardonnay vines have undergone gene inactivation to enable them to better defend themselves against downy mildew, a major fungal disease. The trial is being conducted on university land, with plans to expand to another site in the Veneto region. Researchers aim to gather initial data by 2025, with the potential for experimental winemaking in 2026.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1630-1630"},"PeriodicalIF":33.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02478-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ancient and versatile CRISPR–Cas nuclease created with ancestral sequence reconstruction","authors":"","doi":"10.1038/s41587-024-02468-w","DOIUrl":"https://doi.org/10.1038/s41587-024-02468-w","url":null,"abstract":"Ancestral sequence reconstruction enables the identification and synthesis of ReChb, an ancient form of CRISPR–Cas12a with a highly versatile functionality. ReChb can target any nucleic acid, with minimal restrictions, making it a multipurpose tool for genome editing and genetic diagnostics.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"17 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580346","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}
Thomas D. Avery, Jiahe Li, Dion J. L. Turner, Mohd S. U. Rasheed, Fisher R. Cherry, Damian L. Stachura, Fátima Rivera-Escalera, David M. Ruiz, Michael J. Lacagnina, Caitlyn M. Gaffney, Clarissa Aguilar, Jingxian Yu, Yang Wang, Huan Xie, Dong Liang, Andrew J. Shepherd, Andrew D. Abell, Peter M. Grace
{"title":"Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders","authors":"Thomas D. Avery, Jiahe Li, Dion J. L. Turner, Mohd S. U. Rasheed, Fisher R. Cherry, Damian L. Stachura, Fátima Rivera-Escalera, David M. Ruiz, Michael J. Lacagnina, Caitlyn M. Gaffney, Clarissa Aguilar, Jingxian Yu, Yang Wang, Huan Xie, Dong Liang, Andrew J. Shepherd, Andrew D. Abell, Peter M. Grace","doi":"10.1038/s41587-024-02460-4","DOIUrl":"https://doi.org/10.1038/s41587-024-02460-4","url":null,"abstract":"<p>Treatment of diseases of oxidative stress through activation of the antioxidant nuclear factor E2-related factor 2 (NRF2) is limited by systemic side effects. We chemically functionalize the NRF2 activator monomethyl fumarate to require Baeyer–Villiger oxidation for release of the active drug at sites of oxidative stress. This prodrug reverses chronic pain in mice with reduced side effects and could be applied to other disorders of oxidative stress.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"23 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574320","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":"CRISPR Nobelists surrender their own European patents","authors":"Charlotte Harrison","doi":"10.1038/s41587-024-02472-0","DOIUrl":"10.1038/s41587-024-02472-0","url":null,"abstract":"A strategic move by lawyers acting for Doudna and Charpentier is the latest twist in the battleground for CRISPR–Cas9 technology.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1629-1629"},"PeriodicalIF":33.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02472-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Frank Erasmus, Laura Spector, Fortunato Ferrara, Roberto DiNiro, Thomas J. Pohl, Katheryn Perea-Schmittle, Wei Wang, Peter M. Tessier, Crystal Richardson, Laure Turner, Sumit Kumar, Daniel Bedinger, Pietro Sormanni, Monica L. Fernández-Quintero, Andrew B. Ward, Johannes R. Loeffler, Olivia M. Swanson, Charlotte M. Deane, Matthew I. J. Raybould, Andreas Evers, Carolin Sellmann, Sharrol Bachas, Jeff Ruffolo, Horacio G. Nastri, Karthik Ramesh, Jesper Sørensen, Rebecca Croasdale-Wood, Oliver Hijano, Camila Leal-Lopes, Melody Shahsavarian, Yu Qiu, Paolo Marcatili, Erik Vernet, Rahmad Akbar, Simon Friedensohn, Rick Wagner, Vinodh babu Kurella, Shipra Malhotra, Satyendra Kumar, Patrick Kidger, Juan C. Almagro, Eric Furfine, Marty Stanton, Christilyn P. Graff, Santiago David Villalba, Florian Tomszak, Andre A. R. Teixeira, Elizabeth Hopkins, Molly Dovner, Sara D’Angelo, Andrew R. M. Bradbury
{"title":"AIntibody: an experimentally validated in silico antibody discovery design challenge","authors":"M. Frank Erasmus, Laura Spector, Fortunato Ferrara, Roberto DiNiro, Thomas J. Pohl, Katheryn Perea-Schmittle, Wei Wang, Peter M. Tessier, Crystal Richardson, Laure Turner, Sumit Kumar, Daniel Bedinger, Pietro Sormanni, Monica L. Fernández-Quintero, Andrew B. Ward, Johannes R. Loeffler, Olivia M. Swanson, Charlotte M. Deane, Matthew I. J. Raybould, Andreas Evers, Carolin Sellmann, Sharrol Bachas, Jeff Ruffolo, Horacio G. Nastri, Karthik Ramesh, Jesper Sørensen, Rebecca Croasdale-Wood, Oliver Hijano, Camila Leal-Lopes, Melody Shahsavarian, Yu Qiu, Paolo Marcatili, Erik Vernet, Rahmad Akbar, Simon Friedensohn, Rick Wagner, Vinodh babu Kurella, Shipra Malhotra, Satyendra Kumar, Patrick Kidger, Juan C. Almagro, Eric Furfine, Marty Stanton, Christilyn P. Graff, Santiago David Villalba, Florian Tomszak, Andre A. R. Teixeira, Elizabeth Hopkins, Molly Dovner, Sara D’Angelo, Andrew R. M. Bradbury","doi":"10.1038/s41587-024-02469-9","DOIUrl":"10.1038/s41587-024-02469-9","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1637-1642"},"PeriodicalIF":33.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02469-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What will it take to get miRNA therapies to market?","authors":"","doi":"10.1038/s41587-024-02480-0","DOIUrl":"10.1038/s41587-024-02480-0","url":null,"abstract":"The Nobel Prize in medicine was awarded for the discovery of miRNA, but miRNA therapeutics have a long way to go before they outcompete other therapies.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1623-1624"},"PeriodicalIF":33.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02480-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew J. Szarzanowicz, Lucas M. Waldburger, Michael Busche, Gina M. Geiselman, Liam D. Kirkpatrick, Alexander J. Kehl, Claudine Tahmin, Rita C. Kuo, Joshua McCauley, Hamreet Pannu, Ruoming Cui, Shuying Liu, Nathan J. Hillson, Jacob O. Brunkard, Jay D. Keasling, John M. Gladden, Mitchell G. Thompson, Patrick M. Shih
{"title":"Binary vector copy number engineering improves Agrobacterium-mediated transformation","authors":"Matthew J. Szarzanowicz, Lucas M. Waldburger, Michael Busche, Gina M. Geiselman, Liam D. Kirkpatrick, Alexander J. Kehl, Claudine Tahmin, Rita C. Kuo, Joshua McCauley, Hamreet Pannu, Ruoming Cui, Shuying Liu, Nathan J. Hillson, Jacob O. Brunkard, Jay D. Keasling, John M. Gladden, Mitchell G. Thompson, Patrick M. Shih","doi":"10.1038/s41587-024-02462-2","DOIUrl":"https://doi.org/10.1038/s41587-024-02462-2","url":null,"abstract":"<p>The copy number of a plasmid is linked to its functionality, yet there have been few attempts to optimize higher-copy-number mutants for use across diverse origins of replication in different hosts. We use a high-throughput growth-coupled selection assay and a directed evolution approach to rapidly identify origin of replication mutations that influence copy number and screen for mutants that improve <i>Agrobacterium</i>-mediated transformation (AMT) efficiency. By introducing these mutations into binary vectors within the plasmid backbone used for AMT, we observe improved transient transformation of <i>Nicotiana benthamiana</i> in four diverse tested origins (pVS1, RK2, pSa and BBR1). For the best-performing origin, pVS1, we isolate higher-copy-number variants that increase stable transformation efficiencies by 60–100% in <i>Arabidopsis thaliana</i> and 390% in the oleaginous yeast <i>Rhodosporidium toruloides</i>. Our work provides an easily deployable framework to generate plasmid copy number variants that will enable greater precision in prokaryotic genetic engineering, in addition to improving AMT efficiency.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"33 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574319","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}
Josh Tycko, Mike V. Van, Aradhana, Nicole DelRosso, Hanrong Ye, David Yao, Raeline Valbuena, Alun Vaughan-Jackson, Xiaoshu Xu, Connor Ludwig, Kaitlyn Spees, Katherine Liu, Mingxin Gu, Venya Khare, Adi Xiyal Mukund, Peter H. Suzuki, Sophia Arana, Catherine Zhang, Peter P. Du, Thea S. Ornstein, Gaelen T. Hess, Roarke A. Kamber, Lei S. Qi, Ahmad S. Khalil, Lacramioara Bintu, Michael C. Bassik
{"title":"Development of compact transcriptional effectors using high-throughput measurements in diverse contexts","authors":"Josh Tycko, Mike V. Van, Aradhana, Nicole DelRosso, Hanrong Ye, David Yao, Raeline Valbuena, Alun Vaughan-Jackson, Xiaoshu Xu, Connor Ludwig, Kaitlyn Spees, Katherine Liu, Mingxin Gu, Venya Khare, Adi Xiyal Mukund, Peter H. Suzuki, Sophia Arana, Catherine Zhang, Peter P. Du, Thea S. Ornstein, Gaelen T. Hess, Roarke A. Kamber, Lei S. Qi, Ahmad S. Khalil, Lacramioara Bintu, Michael C. Bassik","doi":"10.1038/s41587-024-02442-6","DOIUrl":"https://doi.org/10.1038/s41587-024-02442-6","url":null,"abstract":"<p>Transcriptional effectors are protein domains known to activate or repress gene expression; however, a systematic understanding of which effector domains regulate transcription across genomic, cell type and DNA-binding domain (DBD) contexts is lacking. Here we develop dCas9-mediated high-throughput recruitment (HT-recruit), a pooled screening method for quantifying effector function at endogenous target genes and test effector function for a library containing 5,092 nuclear protein Pfam domains across varied contexts. We also map context dependencies of effectors drawn from unannotated protein regions using a larger library tiling chromatin regulators and transcription factors. We find that many effectors depend on target and DBD contexts, such as HLH domains that can act as either activators or repressors. To enable efficient perturbations, we select context-robust domains, including ZNF705 KRAB, that improve CRISPRi tools to silence promoters and enhancers. We engineer a compact human activator called NFZ, by combining NCOA3, FOXO3 and ZNF473 domains, which enables efficient CRISPRa with better viral delivery and inducible control of chimeric antigen receptor T cells.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"35 6 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562135","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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