Nature biotechnology最新文献_第8页

Increasing intracellular dNTP levels improves prime editing efficiency 增加细胞内 dNTP 水平可提高素材编辑效率

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-25 DOI: 10.1038/s41587-024-02405-x

Pengpeng Liu, Karthikeyan Ponnienselvan, Thomas Nyalile, Sarah Oikemus, Anya T. Joynt, Sukanya Iyer, Karen Kelly, Dongsheng Guo, Pyae P. Kyawe, Emma Vanderleeden, Sambra D. Redick, Lei Huang, Zexiang Chen, Jeong Min Lee, Celia A. Schiffer, David M. Harlan, Jennifer P. Wang, Charles P. Emerson, Nathan D. Lawson, Jonathan K. Watts, Erik J. Sontheimer, Jeremy Luban, Scot A. Wolfe

引用次数: 0

Multistate and functional protein design using RoseTTAFold sequence space diffusion 利用 RoseTTAFold 序列空间扩散进行多态和功能蛋白质设计

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-25 DOI: 10.1038/s41587-024-02395-w

Sidney Lyayuga Lisanza, Jacob Merle Gershon, Samuel W. K. Tipps, Jeremiah Nelson Sims, Lucas Arnoldt, Samuel J. Hendel, Miriam K. Simma, Ge Liu, Muna Yase, Hongwei Wu, Claire D. Tharp, Xinting Li, Alex Kang, Evans Brackenbrough, Asim K. Bera, Stacey Gerben, Bruce J. Wittmann, Andrew C. McShan, David Baker

{"title":"Multistate and functional protein design using RoseTTAFold sequence space diffusion","authors":"Sidney Lyayuga Lisanza, Jacob Merle Gershon, Samuel W. K. Tipps, Jeremiah Nelson Sims, Lucas Arnoldt, Samuel J. Hendel, Miriam K. Simma, Ge Liu, Muna Yase, Hongwei Wu, Claire D. Tharp, Xinting Li, Alex Kang, Evans Brackenbrough, Asim K. Bera, Stacey Gerben, Bruce J. Wittmann, Andrew C. McShan, David Baker","doi":"10.1038/s41587-024-02395-w","DOIUrl":"https://doi.org/10.1038/s41587-024-02395-w","url":null,"abstract":"Protein denoising diffusion probabilistic models are used for the de novo generation of protein backbones but are limited in their ability to guide generation of proteins with sequence-specific attributes and functional properties. To overcome this limitation, we developed ProteinGenerator (PG), a sequence space diffusion model based on RoseTTAFold that simultaneously generates protein sequences and structures. Beginning from a noised sequence representation, PG generates sequence and structure pairs by iterative denoising, guided by desired sequence and structural protein attributes. We designed thermostable proteins with varying amino acid compositions and internal sequence repeats and cage bioactive peptides, such as melittin. By averaging sequence logits between diffusion trajectories with distinct structural constraints, we designed multistate parent–child protein triples in which the same sequence folds to different supersecondary structures when intact in the parent versus split into two child domains. PG design trajectories can be guided by experimental sequence–activity data, providing a general approach for integrated computational and experimental optimization of protein function.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317065","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

Plastic-eating bacteria boost growing business of bioremediation 吃塑料的细菌促进了生物修复业务的增长

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-09-23 DOI: 10.1038/s41587-024-02401-1

Ben Johnson

引用次数: 0

Scalable and unsupervised discovery from raw sequencing reads using SPLASH2 利用 SPLASH2 从原始测序读数中进行可扩展的无监督发现

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-23 DOI: 10.1038/s41587-024-02381-2

Marek Kokot, Roozbeh Dehghannasiri, Tavor Baharav, Julia Salzman, Sebastian Deorowicz

引用次数: 0

Coordinated, multicellular patterns of transcriptional variation that stratify patient cohorts are revealed by tensor decomposition 张量分解法揭示了使患者群体分层的多细胞转录变异协调模式

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-23 DOI: 10.1038/s41587-024-02411-z

Jonathan Mitchel, M. Grace Gordon, Richard K. Perez, Evan Biederstedt, Raymund Bueno, Chun Jimmie Ye, Peter V. Kharchenko

{"title":"Coordinated, multicellular patterns of transcriptional variation that stratify patient cohorts are revealed by tensor decomposition","authors":"Jonathan Mitchel, M. Grace Gordon, Richard K. Perez, Evan Biederstedt, Raymund Bueno, Chun Jimmie Ye, Peter V. Kharchenko","doi":"10.1038/s41587-024-02411-z","DOIUrl":"https://doi.org/10.1038/s41587-024-02411-z","url":null,"abstract":"Tissue-level and organism-level biological processes often involve the coordinated action of multiple distinct cell types. The recent application of single-cell assays to many individuals should enable the study of how donor-level variation in one cell type is linked to that in other cell types. Here we introduce a computational approach called single-cell interpretable tensor decomposition (scITD) to identify common axes of interindividual variation by considering joint expression variation across multiple cell types. scITD combines expression matrices from each cell type into a higher-order matrix and factorizes the result using the Tucker tensor decomposition. Applying scITD to single-cell RNA-sequencing data on 115 persons with lupus and 83 persons with coronavirus disease 2019, we identify patterns of coordinated cellular activity linked to disease severity and specific phenotypes, such as lupus nephritis. scITD results also implicate specific signaling pathways likely mediating coordination between cell types. Overall, scITD offers a tool for understanding the covariation of cell states across individuals, which can yield insights into the complex processes that define and stratify disease.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276917","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

Chemical and topological design of multicapped mRNA and capped circular RNA to augment translation 多封端 mRNA 和封端环形 RNA 的化学和拓扑设计，以增强翻译能力

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-23 DOI: 10.1038/s41587-024-02393-y

Hongyu Chen, Dangliang Liu, Abhishek Aditham, Jianting Guo, Jiahao Huang, Franklin Kostas, Kamal Maher, Mirco J. Friedrich, Ramnik J. Xavier, Feng Zhang, Xiao Wang

{"title":"Chemical and topological design of multicapped mRNA and capped circular RNA to augment translation","authors":"Hongyu Chen, Dangliang Liu, Abhishek Aditham, Jianting Guo, Jiahao Huang, Franklin Kostas, Kamal Maher, Mirco J. Friedrich, Ramnik J. Xavier, Feng Zhang, Xiao Wang","doi":"10.1038/s41587-024-02393-y","DOIUrl":"https://doi.org/10.1038/s41587-024-02393-y","url":null,"abstract":"Protein and vaccine therapies based on mRNA would benefit from an increase in translation capacity. Here, we report a method to augment translation named ligation-enabled mRNA–oligonucleotide assembly (LEGO). We systematically screen different chemotopological motifs and find that a branched mRNA cap effectively initiates translation on linear or circular mRNAs without internal ribosome entry sites. Two types of chemical modification, locked nucleic acid (LNA) N7-methylguanosine modifications on the cap and LNA + 5 × 2′ O-methyl on the 5′ untranslated region, enhance RNA–eukaryotic translation initiation factor (eIF4E–eIF4G) binding and RNA stability against decapping in vitro. Through multidimensional chemotopological engineering of dual-capped mRNA and capped circular RNA, we enhanced mRNA protein production by up to tenfold in vivo, resulting in 17-fold and 3.7-fold higher antibody production after prime and boost doses in a severe acute respiratory syndrome coronavirus 2 vaccine setting, respectively. The LEGO platform opens possibilities to design unnatural RNA structures and topologies beyond canonical linear and circular RNAs for both basic research and therapeutic applications.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276920","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

Building better mRNA for therapeutics 构建更好的 mRNA 用于治疗

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-23 DOI: 10.1038/s41587-024-02424-8

Bei Liu, Tao Pan

引用次数: 0

Targeting double-stranded nucleic acids using the λExo–pDNA system 利用 λExo-pDNA 系统靶向双链核酸

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-18 DOI: 10.1038/s41587-024-02409-7

引用次数: 0

Bacteriophage λ exonuclease and a 5′-phosphorylated DNA guide allow PAM-independent targeting of double-stranded nucleic acids 噬菌体 λ 外切酶和 5′-磷酸化 DNA 向导可实现双链核酸的 PAM 依赖性靶向

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-18 DOI: 10.1038/s41587-024-02388-9

Shengnan Fu, Junjie Li, Jing Chen, Linghao Zhang, Jiajia Liu, Huiyu Liu, Xin Su

{"title":"Bacteriophage λ exonuclease and a 5′-phosphorylated DNA guide allow PAM-independent targeting of double-stranded nucleic acids","authors":"Shengnan Fu, Junjie Li, Jing Chen, Linghao Zhang, Jiajia Liu, Huiyu Liu, Xin Su","doi":"10.1038/s41587-024-02388-9","DOIUrl":"https://doi.org/10.1038/s41587-024-02388-9","url":null,"abstract":"Sequence-specific recognition of double-stranded nucleic acids is essential for molecular diagnostics and in situ imaging. Clustered regularly interspaced short palindromic repeats and Cas systems rely on protospacer-adjacent motif (PAM)-dependent double-stranded DNA (dsDNA) recognition, limiting the range of targetable sequences and leading to undesired off-target effects. Using single-molecule fluorescence resonance energy transfer analysis, we discover the enzymatic activity of bacteriophage λ exonuclease (λExo). We show binding of 5′-phosphorylated single-stranded DNA (pDNA) to complementary regions on dsDNA and DNA–RNA duplexes, without the need for a PAM-like motif. Upon binding, the λExo–pDNA system catalytically digests the pDNA into nucleotides in the presence of Mg2+. This process is sensitive to mismatches within a wide range of the pDNA-binding region, resulting in exceptional sequence specificity and reduced off-target effects in various applications. The absence of a requirement for a specific motif such as a PAM sequence greatly broadens the range of targets. We demonstrate that the λExo–pDNA system is a versatile tool for molecular diagnostics, DNA computing and gene imaging applications.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236742","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 developmental route to hematopoietic stem cells 造血干细胞的发育途径

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-09-18 DOI: 10.1038/s41587-024-02398-7

Adam C. Wilkinson, Marella F. T. R. de Bruijn

引用次数: 0