Nature biotechnology最新文献_第7页

Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders 治疗氧化应激紊乱的富马酸单甲酯的部位特异性药物释放

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-04 DOI: 10.1038/s41587-024-02460-4

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

引用次数: 0

CRISPR Nobelists surrender their own European patents CRISPR 诺贝尔奖获得者交出自己的欧洲专利

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-11-04 DOI: 10.1038/s41587-024-02472-0

Charlotte Harrison

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AIntibody: an experimentally validated in silico antibody discovery design challenge AIntibody：经实验验证的硅学抗体发现设计挑战

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-11-04 DOI: 10.1038/s41587-024-02469-9

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

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What will it take to get miRNA therapies to market? 如何才能将 miRNA 疗法推向市场？

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-11-04 DOI: 10.1038/s41587-024-02480-0

引用次数: 0

Binary vector copy number engineering improves Agrobacterium-mediated transformation 二元载体拷贝数工程改进了农杆菌介导的转化

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-04 DOI: 10.1038/s41587-024-02462-2

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":"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 Agrobacterium-mediated transformation (AMT) efficiency. By introducing these mutations into binary vectors within the plasmid backbone used for AMT, we observe improved transient transformation of Nicotiana benthamiana 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 Arabidopsis thaliana and 390% in the oleaginous yeast Rhodosporidium toruloides. 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.","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}

引用次数: 0

Development of compact transcriptional effectors using high-throughput measurements in diverse contexts 在不同背景下利用高通量测量开发紧凑型转录效应因子

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-01 DOI: 10.1038/s41587-024-02442-6

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":"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.","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}

引用次数: 0

A resurrected ancestor of Cas12a expands target access and substrate recognition for nucleic acid editing and detection Cas12a 的复活祖先扩大了核酸编辑和检测的目标访问和底物识别范围

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-31 DOI: 10.1038/s41587-024-02461-3

Ylenia Jabalera, Igor Tascón, Sara Samperio, Jorge P. López-Alonso, Monika Gonzalez-Lopez, Ana M. Aransay, Guillermo Abascal-Palacios, Chase L. Beisel, Iban Ubarretxena-Belandia, Raul Perez-Jimenez

{"title":"A resurrected ancestor of Cas12a expands target access and substrate recognition for nucleic acid editing and detection","authors":"Ylenia Jabalera, Igor Tascón, Sara Samperio, Jorge P. López-Alonso, Monika Gonzalez-Lopez, Ana M. Aransay, Guillermo Abascal-Palacios, Chase L. Beisel, Iban Ubarretxena-Belandia, Raul Perez-Jimenez","doi":"10.1038/s41587-024-02461-3","DOIUrl":"https://doi.org/10.1038/s41587-024-02461-3","url":null,"abstract":"The properties of Cas12a nucleases constrict the range of accessible targets and their applications. In this study, we applied ancestral sequence reconstruction (ASR) to a set of Cas12a orthologs from hydrobacteria to reconstruct a common ancestor, ReChb, characterized by near-PAMless targeting and the recognition of diverse nucleic acid activators and collateral substrates. ReChb shares 53% sequence identity with the closest Cas12a ortholog but no longer requires a T-rich PAM and can achieve genome editing in human cells at sites inaccessible to the natural FnCas12a or the engineered and PAM-flexible enAsCas12a. Furthermore, ReChb can be triggered not only by double-stranded DNA but also by single-stranded RNA and DNA targets, leading to non-specific collateral cleavage of all three nucleic acid substrates with similar efficiencies. Finally, tertiary and quaternary structures of ReChb obtained by cryogenic electron microscopy reveal the molecular details underlying its expanded biophysical activities. Overall, ReChb expands the application space of Cas12a nucleases and underscores the potential of ASR for enhancing CRISPR technologies.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"111 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555820","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}

引用次数: 0

Comprehensive genome analysis and variant detection at scale using DRAGEN 使用 DRAGEN 进行大规模综合基因组分析和变异检测

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-25 DOI: 10.1038/s41587-024-02382-1

Sairam Behera, Severine Catreux, Massimiliano Rossi, Sean Truong, Zhuoyi Huang, Michael Ruehle, Arun Visvanath, Gavin Parnaby, Cooper Roddey, Vitor Onuchic, Andrea Finocchio, Daniel L. Cameron, Adam English, Shyamal Mehtalia, James Han, Rami Mehio, Fritz J. Sedlazeck

{"title":"Comprehensive genome analysis and variant detection at scale using DRAGEN","authors":"Sairam Behera, Severine Catreux, Massimiliano Rossi, Sean Truong, Zhuoyi Huang, Michael Ruehle, Arun Visvanath, Gavin Parnaby, Cooper Roddey, Vitor Onuchic, Andrea Finocchio, Daniel L. Cameron, Adam English, Shyamal Mehtalia, James Han, Rami Mehio, Fritz J. Sedlazeck","doi":"10.1038/s41587-024-02382-1","DOIUrl":"https://doi.org/10.1038/s41587-024-02382-1","url":null,"abstract":"Research and medical genomics require comprehensive, scalable methods for the discovery of novel disease targets, evolutionary drivers and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size or location. Here we present DRAGEN, which uses multigenome mapping with pangenome references, hardware acceleration and machine learning-based variant detection to provide insights into individual genomes, with ~30 min of computation time from raw reads to variant detection. DRAGEN outperforms current state-of-the-art methods in speed and accuracy across all variant types (single-nucleotide variations, insertions or deletions, short tandem repeats, structural variations and copy number variations) and incorporates specialized methods for analysis of medically relevant genes. We demonstrate the performance of DRAGEN across 3,202 whole-genome sequencing datasets by generating fully genotyped multisample variant call format files and demonstrate its scalability, accuracy and innovation to further advance the integration of comprehensive genomics. Overall, DRAGEN marks a major milestone in sequencing data analysis and will provide insights across various diseases, including Mendelian and rare diseases, with a highly comprehensive and scalable platform.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"14 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489255","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}

引用次数: 0

Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors 金-siRNA超簇可增强原发性和转移性肿瘤立体定向消融放疗的抗肿瘤免疫反应

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-24 DOI: 10.1038/s41587-024-02448-0

Yuyan Jiang, Hongbin Cao, Huaping Deng, Li Guan, Jimpi Langthasa, Deana Rae Crystal Colburg, Stavros Melemenidis, Renee M. Cotton, John Aleman, Xiao-Jing Wang, Edward E. Graves, Anusha Kalbasi, Kanyi Pu, Jianghong Rao, Quynh-Thu Le

{"title":"Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors","authors":"Yuyan Jiang, Hongbin Cao, Huaping Deng, Li Guan, Jimpi Langthasa, Deana Rae Crystal Colburg, Stavros Melemenidis, Renee M. Cotton, John Aleman, Xiao-Jing Wang, Edward E. Graves, Anusha Kalbasi, Kanyi Pu, Jianghong Rao, Quynh-Thu Le","doi":"10.1038/s41587-024-02448-0","DOIUrl":"https://doi.org/10.1038/s41587-024-02448-0","url":null,"abstract":"Strategies to enhance the anti-tumor immune response of stereotactic ablative radiotherapy (SABR) at primary tumors and abscopal sites are under intensive investigation. Here we report a metabolizable binary supracluster (BSCgal) that combines gold nanoclusters as radiosensitizing adjuvants with small interfering RNA (siRNA) targeting the immunosuppressive mediator galectin-1 (Gal-1). BSCgal comprises reversibly crosslinked cationic gold nanoclusters and siRNA complexes in a polymer matrix that biodegrades over weeks, facilitating clearance (90.3% in vivo clearance at 4 weeks) to reduce toxicity. The particle size well above the renal filtration threshold facilitates passive delivery to tumors. Using mouse models of head and neck cancer, we show that BSCgal augments the radiodynamic and immunotherapeutic effects of SABR at the primary and metastatic tumors by promoting tumor-inhibitory leukocytes, upregulating cytotoxic granzyme B and reducing immunosuppressive cell populations. It outperforms SABR plus Gal-1 antagonists, chemoradiation drug cisplatin or PD-1 inhibitor. This work presents a translatable strategy to converge focal radiosensitization with targeted immune checkpoint silencing for personalized radioimmunotherapy.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"235 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488476","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}

引用次数: 0

A structurally informed human protein–protein interactome reveals proteome-wide perturbations caused by disease mutations 从结构上了解人类蛋白质-蛋白质相互作用组，揭示疾病突变引起的全蛋白质组扰动

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-24 DOI: 10.1038/s41587-024-02428-4

Dapeng Xiong, Yunguang Qiu, Junfei Zhao, Yadi Zhou, Dongjin Lee, Shobhita Gupta, Mateo Torres, Weiqiang Lu, Siqi Liang, Jin Joo Kang, Charis Eng, Joseph Loscalzo, Feixiong Cheng, Haiyuan Yu

{"title":"A structurally informed human protein–protein interactome reveals proteome-wide perturbations caused by disease mutations","authors":"Dapeng Xiong, Yunguang Qiu, Junfei Zhao, Yadi Zhou, Dongjin Lee, Shobhita Gupta, Mateo Torres, Weiqiang Lu, Siqi Liang, Jin Joo Kang, Charis Eng, Joseph Loscalzo, Feixiong Cheng, Haiyuan Yu","doi":"10.1038/s41587-024-02428-4","DOIUrl":"https://doi.org/10.1038/s41587-024-02428-4","url":null,"abstract":"To assist the translation of genetic findings to disease pathobiology and therapeutics discovery, we present an ensemble deep learning framework, termed PIONEER (Protein–protein InteractiOn iNtErfacE pRediction), that predicts protein-binding partner-specific interfaces for all known protein interactions in humans and seven other common model organisms to generate comprehensive structurally informed protein interactomes. We demonstrate that PIONEER outperforms existing state-of-the-art methods and experimentally validate its predictions. We show that disease-associated mutations are enriched in PIONEER-predicted protein–protein interfaces and explore their impact on disease prognosis and drug responses. We identify 586 significant protein–protein interactions (PPIs) enriched with PIONEER-predicted interface somatic mutations (termed oncoPPIs) from analysis of approximately 11,000 whole exomes across 33 cancer types and show significant associations of oncoPPIs with patient survival and drug responses. PIONEER, implemented as both a web server platform and a software package, identifies functional consequences of disease-associated alleles and offers a deep learning tool for precision medicine at multiscale interactome network levels.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"23 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488475","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}

引用次数: 0