Nature biotechnology最新文献_第3页

Mismatch repair inhibitors lift off in Huntington’s 错配修复抑制剂在亨廷顿氏症中大显身手

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02646-4

引用次数: 0

Virtual cells for predictive immunotherapy 用于预测性免疫疗法的虚拟细胞

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02583-2

Daniel R. Bergman, Elana J. Fertig

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FDA approves Alnylam’s anti-amyloid RNAi drug for cardiomyopathy FDA 批准 Alnylam 的抗淀粉样蛋白 RNAi 药物治疗心肌病

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02656-2

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Hyperspectral reporters for long-distance and wide-area detection of gene expression in living bacteria 用于远距离和大范围检测活细菌基因表达的高光谱报告器

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-11 DOI: 10.1038/s41587-025-02622-y

Yonatan Chemla, Itai Levin, Yueyang Fan, Anna A. Johnson, Connor W. Coley, Christopher A. Voigt

{"title":"Hyperspectral reporters for long-distance and wide-area detection of gene expression in living bacteria","authors":"Yonatan Chemla, Itai Levin, Yueyang Fan, Anna A. Johnson, Connor W. Coley, Christopher A. Voigt","doi":"10.1038/s41587-025-02622-y","DOIUrl":"https://doi.org/10.1038/s41587-025-02622-y","url":null,"abstract":"Genetically encoded reporters are suitable for short-distance imaging in the laboratory but not for scanning wide outdoor areas from a distance. Here we introduce hyperspectral reporters (HSRs) designed for hyperspectral imaging cameras that are commonly mounted on unmanned aerial vehicles and satellites. HSR genes encode enzymes that produce a molecule with a unique absorption signature that can be reliably distinguished in hyperspectral images. Quantum mechanical simulations of 20,170 metabolites identified candidate HSRs, leading to the selection of biliverdin IXα and bacteriochlorophyll a for their distinct absorption spectra and biosynthetic feasibility. These genes were integrated into chemical sensor circuits in soil (Pseudomonas putida) and aquatic (Rubrivivax gelatinosus) bacteria. The bacteria were detectable outdoors under ambient light from up to 90 m in a single 4,000-m2 hyperspectral image taken using fixed and unmanned aerial vehicle-mounted cameras. The dose–response functions of the chemical sensors were measured remotely. HSRs enable large-scale studies and applications in ecology, agriculture, environmental monitoring, forensics and defense.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"16 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819378","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

Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-04 DOI: 10.1038/s41587-025-02618-8

Ayse G. Keskus, Asher Bryant, Tanveer Ahmad, Byunggil Yoo, Sergey Aganezov, Anton Goretsky, Ataberk Donmez, Lisa A. Lansdon, Isabel Rodriguez, Jimin Park, Yuelin Liu, Xiwen Cui, Joshua Gardner, Brandy McNulty, Samuel Sacco, Jyoti Shetty, Yongmei Zhao, Bao Tran, Giuseppe Narzisi, Adrienne Helland, Daniel E. Cook, Pi-Chuan Chang, Alexey Kolesnikov, Andrew Carroll, Erin K. Molloy, Chengpeng Bi, Adam Walter, Margaret Gibson, Irina Pushel, Erin Guest, Tomi Pastinen, Kishwar Shafin, Karen H. Miga, Salem Malikic, Chi-Ping Day, Nicolas Robine, Cenk Sahinalp, Michael Dean, Midhat S. Farooqi, Benedict Paten, Mikhail Kolmogorov

{"title":"Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing","authors":"Ayse G. Keskus, Asher Bryant, Tanveer Ahmad, Byunggil Yoo, Sergey Aganezov, Anton Goretsky, Ataberk Donmez, Lisa A. Lansdon, Isabel Rodriguez, Jimin Park, Yuelin Liu, Xiwen Cui, Joshua Gardner, Brandy McNulty, Samuel Sacco, Jyoti Shetty, Yongmei Zhao, Bao Tran, Giuseppe Narzisi, Adrienne Helland, Daniel E. Cook, Pi-Chuan Chang, Alexey Kolesnikov, Andrew Carroll, Erin K. Molloy, Chengpeng Bi, Adam Walter, Margaret Gibson, Irina Pushel, Erin Guest, Tomi Pastinen, Kishwar Shafin, Karen H. Miga, Salem Malikic, Chi-Ping Day, Nicolas Robine, Cenk Sahinalp, Michael Dean, Midhat S. Farooqi, Benedict Paten, Mikhail Kolmogorov","doi":"10.1038/s41587-025-02618-8","DOIUrl":"https://doi.org/10.1038/s41587-025-02618-8","url":null,"abstract":"For the detection of somatic structural variation (SV) in cancer genomes, long-read sequencing is advantageous over short-read sequencing with respect to mappability and variant phasing. However, most current long-read SV detection methods are not developed for the analysis of tumor genomes characterized by complex rearrangements and heterogeneity. Here, we present Severus, a breakpoint graph-based algorithm for somatic SV calling from long-read cancer sequencing. Severus works with matching normal samples, supports unbalanced cancer karyotypes, can characterize complex multibreak SV patterns and produces haplotype-specific calls. On a comprehensive multitechnology cell line panel, Severus consistently outperforms other long-read and short-read methods in terms of SV detection F1 score (harmonic mean of the precision and recall). We also illustrate that compared to long-read methods, short-read sequencing systematically misses certain classes of somatic SVs, such as insertions or clustered rearrangements. We apply Severus to several clinical cases of pediatric leukemia/lymphoma, revealing clinically relevant cryptic rearrangements missed by standard genomic panels.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"183 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775369","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

Scalable spatial transcriptomics through computational array reconstruction 通过计算阵列重建实现可扩展的空间转录组学

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-03 DOI: 10.1038/s41587-025-02612-0

Chenlei Hu, Mehdi Borji, Giovanni J. Marrero, Vipin Kumar, Jackson A. Weir, Sachin V. Kammula, Evan Z. Macosko, Fei Chen

引用次数: 0

Improved RNA base editing with guide RNAs mimicking highly edited endogenous ADAR substrates

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-03 DOI: 10.1038/s41587-025-02628-6

Yuanfan Sun, Yong Cao, Yulong Song, Jin Li, Yongheng Hou, Wen Huang, Guodong Xie, Wenbing Yang, Rui Zhang

{"title":"Improved RNA base editing with guide RNAs mimicking highly edited endogenous ADAR substrates","authors":"Yuanfan Sun, Yong Cao, Yulong Song, Jin Li, Yongheng Hou, Wen Huang, Guodong Xie, Wenbing Yang, Rui Zhang","doi":"10.1038/s41587-025-02628-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02628-6","url":null,"abstract":"Adenosine deaminase acting on RNA (ADAR)-mediated RNA base editing offers a safer alternative to genome editing for specific clinical applications because of nonpermanent editing of targets. Current guide RNA (gRNA) designs feature a fully complementary specificity domain with an A–C mismatch at the targeted adenosine. However, perfectly matched dsRNA is not the most effective ADAR substrate. Here we introduce MIRROR (mimicking inverted repeats to recruit ADARs using engineered oligoribonucleotides), an approach that implements structural motifs derived from highly edited inverted Alu repeats in human tissues to enable rational gRNA design for ADAR recruitment. We demonstrated that MIRROR is applicable to both short chemically synthesized gRNAs with modifications and long biologically generated gRNAs and surpasses current state-of-the-art approaches in both gRNA forms. It enhances editing efficiency by up to 5.7-fold in multiple human cell types and primary hepatocytes from an alpha-1 antitrypsin deficiency mouse model. Our findings improve programmable RNA editing in vitro and in vivo by rational design through the screening of highly edited natural substrate mimics.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"57 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766563","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

Openness guides discovery 开放引导发现

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-02 DOI: 10.1038/s41587-025-02635-7

Itai Yanai, Martin J. Lercher

{"title":"Openness guides discovery","authors":"Itai Yanai, Martin J. Lercher","doi":"10.1038/s41587-025-02635-7","DOIUrl":"https://doi.org/10.1038/s41587-025-02635-7","url":null,"abstract":"In reality, research projects grow through an evolutionary process. Variation — the substrate of evolution — is provided through the emergence of new questions and avenues of investigation. The research team must then choose which directions to pursue, a process akin to natural selection1. Along with this evolution at the macro-scale, a much more orderly process is required at the micro-scale. Within each step, thoughtful study design leads to robust experiments and analyses. This complementarity between evolution and design best encapsulates the process of discovery: in ‘night science’ we evolve ideas for the next step, while ‘day science’ tests them2.A project’s evolutionary history is generally obscured in the resulting scientific publication. The publication’s function is to justify and communicate the project’s main results; it is not a historical account. Instead of recounting all of the project’s dried-up branches, publications zoom in on a single lineage in its evolution: the steps that led to the most interesting result (Fig. 1c). Publications typically describe the discovery as it ideally should have happened, reporting only the evidence relevant to the proposed claims3.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"37 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758447","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

The emerging landscape of engineered bacteria cancer therapies 工程菌癌症疗法的新兴前景

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-01 DOI: 10.1038/s41587-025-02623-x

Edward R. Ballister, Alexander Michels, Rosa L. Vincent, Lior Kreindler, Sreyan Chowdhury, Samik Upadhaya, Ana Rosa Saez-Ibañez, Tao Tu, Juraj Gottweis, Tal Danino

引用次数: 0

Circular RNA aptamers targeting neuroinflammation ameliorate Alzheimer disease phenotypes in mouse models

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-03-31 DOI: 10.1038/s41587-025-02624-w

Xin Feng, Bo-Wen Jiang, Si-Nan Zhai, Chu-Xiao Liu, Hao Wu, Bang-Qi Zhu, Meng-Yuan Wei, Jia Wei, Li Yang, Ling-Ling Chen

{"title":"Circular RNA aptamers targeting neuroinflammation ameliorate Alzheimer disease phenotypes in mouse models","authors":"Xin Feng, Bo-Wen Jiang, Si-Nan Zhai, Chu-Xiao Liu, Hao Wu, Bang-Qi Zhu, Meng-Yuan Wei, Jia Wei, Li Yang, Ling-Ling Chen","doi":"10.1038/s41587-025-02624-w","DOIUrl":"https://doi.org/10.1038/s41587-025-02624-w","url":null,"abstract":"Alzheimer disease (AD) therapy may benefit from optimized approaches to inhibit neuroinflammation. Small-molecule inhibitors of the proinflammatory molecule double-stranded RNA (dsRNA)-activated protein kinase R (PKR) have efficacy in AD models but their utility is compromised by adverse side effects. Here, we target PKR in two mouse models of AD using circular RNAs containing short double-stranded regions (ds-cRNAs), which are structurally similar to what we used previously to target PKR in psoriasis models. We show that the intrahippocampal injection of ds-cRNAs to neurons and microglia by adeno-associated virus (AAV) effectively dampens excessive PKR activity with minimal toxicity, accompanied by reduced neuroinflammation and amyloid-β plaques. We also deliver ds-cRNAs to the whole brain through intravenous injection of AAV-PHP.eB, which crosses the blood–brain barrier, resulting in neuroprotection and enhanced capability of spatial learning and memory in AD mouse models. The delivery of ds-cRNAs at different progressive stages of AD alleviates disease phenotypes, with therapeutic effects sustained for at least 6 months after a single administration.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"4 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736577","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