Nature biotechnology最新文献_第10页

Author Correction: Sustained nitric oxide production by engineered E. coli remodels the tumor microenvironment and potentiates immunotherapy. 作者更正：工程大肠杆菌持续产生一氧化氮重塑肿瘤微环境并增强免疫治疗。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-07-06 DOI: 10.1038/s41587-026-03247-5

Shuyu Xu, Tianjiao Zhang, Yang Song, Mengxin Wang, Ruiqi Wu, Mofan Li, Haonan Wang, Xinxin Xie, Qingfeng Chen, Xiaotu Ma, Xiaolong Liang

引用次数: 0

Author Correction: Improved RNA base editing with guide RNAs mimicking highly edited endogenous ADAR substrates. 作者更正：使用模仿高度编辑的内源性ADAR底物的引导RNA改进RNA碱基编辑。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-07-03 DOI: 10.1038/s41587-026-03246-6

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

引用次数: 0

Unlocking the chemical potential of filamentous fungi using prime editing. 利用启动编辑解锁丝状真菌的化学势。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-07-02 DOI: 10.1038/s41587-026-03219-9

引用次数: 0

A genome-scale CRISPRi perturbation atlas of human induced pluripotent stem cells. 人类诱导多能干细胞的基因组尺度CRISPRi扰动图谱。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-07-01 DOI: 10.1038/s41587-026-03199-w

Sami Nourreddine,Yesh Doctor,Amir Dailamy,Yi-Hung Lee,Jan N Hansen,Rebecca Chinn,Antoine Forget,Benjamin Polacco,Monita Muralidharan,Alina Sigaeva,Sushant Sunder,Emily Pan,Jiahao Gao,Jake Y Chen,Timothy Clark,Jillian Parker,Kirsten Obernier,Christian Metallo,Trey Ideker,Emma Lundberg,Nevan Krogan,Prashant Mali

{"title":"A genome-scale CRISPRi perturbation atlas of human induced pluripotent stem cells.","authors":"Sami Nourreddine,Yesh Doctor,Amir Dailamy,Yi-Hung Lee,Jan N Hansen,Rebecca Chinn,Antoine Forget,Benjamin Polacco,Monita Muralidharan,Alina Sigaeva,Sushant Sunder,Emily Pan,Jiahao Gao,Jake Y Chen,Timothy Clark,Jillian Parker,Kirsten Obernier,Christian Metallo,Trey Ideker,Emma Lundberg,Nevan Krogan,Prashant Mali","doi":"10.1038/s41587-026-03199-w","DOIUrl":"https://doi.org/10.1038/s41587-026-03199-w","url":null,"abstract":"Comprehensively mapping the relationship between genotype and phenotype offers essential insights into how a cell's state arises from its genetic components. Toward this goal, we generated an expressed genome-scale CRISPRi perturbation cell atlas in KOLF2.1J human induced pluripotent stem cells, mapping transcriptional phenotypes associated with 11,692 perturbed genes across >2.5 million single cells. Using correlations among perturbed phenotypes, we created a cell map of the pluripotent state, demonstrating rich recapitulation of functionally related protein complexes. We then explored the atlas to uncover metabolic factor ZBTB41 and pluripotency regulator RNF7, validating their functions through metabolic tracing, immunofluorescence and protein-protein interaction assays. Lastly, we leveraged the atlas to generate a genome-scale screen of A-to-I RNA-editing modulators assayed through direct transcriptome-wide RNA editing, uncovering and mechanistically validating DBR1 as a potent regulator. Taken together, our data provide a comprehensive resource for interrogating the regulatory networks governing pluripotency, which is accessible at https://y-doctor.github.io/KOLF2.1J_Perturbation_Cell_Atlas/ .","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"443 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148365449","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

Prime editing for precise genome engineering and modulation of fungal metabolism. 用于精确基因组工程和真菌代谢调节的初始编辑。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-06-30 DOI: 10.1038/s41587-026-03202-4

Chunxiao Sun, Qiuyue Nie, Naomi Straub, Chris Keum, Yihui Shen, Xue Gao

{"title":"Prime editing for precise genome engineering and modulation of fungal metabolism.","authors":"Chunxiao Sun, Qiuyue Nie, Naomi Straub, Chris Keum, Yihui Shen, Xue Gao","doi":"10.1038/s41587-026-03202-4","DOIUrl":"10.1038/s41587-026-03202-4","url":null,"abstract":"<p><p>Prime editing has not been established in filamentous fungi, which are major ecological contributors and industrial hosts with vast biosynthetic capacity. Here we develop fPE7max, a prime editing platform optimized for fungi, which supports different edit types, including base substitutions and defined small insertions or deletions, with an average editing efficiency approaching 90%, across diverse genomic loci and species. fPE7max further enables larger insertions of up to 1 kb and deletions of up to 10 kb. We perturb upstream open reading frames in the pleiotropic regulator gene, laeA, to modulate metabolic output across multiple fungal species. Metabolomic profiling reveals activation of previously lowly biosynthetic pathways, leading to the identification of 18 metabolites, including 8, to our knowledge, previously unreported structures, 3 of which with cytotoxic activity. These results establish fPE7max as an efficient platform for genome engineering in filamentous fungi and show upstream open reading frame editing as a strategy for modulating endogenous regulatory networks and accessing the fungal chemical repertoire.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361986","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

Editor’s pick: Liberate Bio

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-06-30 DOI: 10.1038/s41587-026-03201-5

Iris Marchal

引用次数: 0

Editor’s pick: Trogenix 编辑选择:Trogenix

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-06-30 DOI: 10.1038/s41587-026-03200-6

Michael Eisenstein

引用次数: 0

Experiment-guided AlphaFold3 resolves measurement-consistent protein ensembles. 实验引导的AlphaFold3解决了测量一致的蛋白质集合。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-06-29 DOI: 10.1038/s41587-026-03166-5

Advaith Maddipatla,Nadav Sellam Bojan,Meital Bojan,Volodymyr Masalitin,Sanketh Vedula,Paul Schanda,Ailie Marx,Alex M Bronstein

{"title":"Experiment-guided AlphaFold3 resolves measurement-consistent protein ensembles.","authors":"Advaith Maddipatla,Nadav Sellam Bojan,Meital Bojan,Volodymyr Masalitin,Sanketh Vedula,Paul Schanda,Ailie Marx,Alex M Bronstein","doi":"10.1038/s41587-026-03166-5","DOIUrl":"https://doi.org/10.1038/s41587-026-03166-5","url":null,"abstract":"AlphaFold3 predicts highly accurate protein structures from sequence but tends to collapse to a single dominant conformation, even when the underlying structure is inherently heterogeneous. Moreover, its predictions are oblivious to experimental conditions that can alter local sequence conformation. In this work, we show that AlphaFold3 can be guided to match data obtained by nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and cryogenic electron microscopy (cryo-EM) experiments and combinations thereof. Our approach can also incorporate data that explicitly report on dynamics, such as site-resolved order parameters. We demonstrate that this methodology generates compact structural ensembles whose ensemble-averaged observables agree with experiment, with fewer distance restraint violations than traditionally resolved NMR structures and with unmodeled alternate conformations uncovered in electron density. This methodology paves the way for experimentally aware predictive models that generate structural ensembles consistent with the measurements, potentially over multiple modalities, and that can be further refined toward thermodynamically grounded ensembles by incorporating energetics.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"8 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349134","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

Retargeted serine integrases for one-step, precise integration of large DNA sequences in human cells. 重靶向丝氨酸整合酶一步，精确整合大的DNA序列在人类细胞。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-06-29 DOI: 10.1038/s41587-026-03186-1

Friedrich Fauser,Sebastian Arangundy-Franklin,Jessica E Davis,Lifeng Liu,Nicola J Schmidt,Luis Rodriguez,Danny F Xia,Nga Nguyen,Yuanyue Zhou,Nicholas A Scarlott,Lynn N Truong,Rakshaa Mureli,Irene S Tan,Satria Sajuthi,Sarah J Hinkley,Bhakti N Kadam,Stephen Lam,Bryan Bourgeois,Emily Tait,Mohammad Qasim,Vishvesha Vaidya,Adeline Chen,Andrew Nguyen,Yuri R Bendaña,David A Shivak,Patrick Li,Andreas Reik,David E Paschon,Gregory D Davis,Jeffrey C Miller

{"title":"Retargeted serine integrases for one-step, precise integration of large DNA sequences in human cells.","authors":"Friedrich Fauser,Sebastian Arangundy-Franklin,Jessica E Davis,Lifeng Liu,Nicola J Schmidt,Luis Rodriguez,Danny F Xia,Nga Nguyen,Yuanyue Zhou,Nicholas A Scarlott,Lynn N Truong,Rakshaa Mureli,Irene S Tan,Satria Sajuthi,Sarah J Hinkley,Bhakti N Kadam,Stephen Lam,Bryan Bourgeois,Emily Tait,Mohammad Qasim,Vishvesha Vaidya,Adeline Chen,Andrew Nguyen,Yuri R Bendaña,David A Shivak,Patrick Li,Andreas Reik,David E Paschon,Gregory D Davis,Jeffrey C Miller","doi":"10.1038/s41587-026-03186-1","DOIUrl":"https://doi.org/10.1038/s41587-026-03186-1","url":null,"abstract":"Serine integrases can precisely integrate large DNA constructs into desired chromosomal sites but only if their natural target site is first installed into the recipient genome. Here, to retarget serine integrases to a desired genomic site, we develop a modular integrase (MINT) system for genome editing. Through a combination of structural modeling, single-round directed evolution and screening in human cells, we retargeted the specificity of the serine integrase Bxb1. We demonstrate the therapeutic potential of the MINT system by retargeting Bxb1 to the human AAVS1 and TRAC loci, where wild-type Bxb1 has no detectable activity. By combining MINT constructs with both known activity-increasing Bxb1 mutants and zinc-finger DNA-binding domains, we achieve efficiencies of 29% at the AAVS1 locus and 35% at the TRAC locus in K562 cells. To further demonstrate clinical potential, we achieved 29% GFP integration efficiencies at the TRAC locus in human T cells.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"30 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349133","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 retargeted recombinase for precise insertion of large DNA. 用于精确插入大DNA的重靶向重组酶。

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-06-29 DOI: 10.1038/s41587-026-03198-x

Frank Buchholz

引用次数: 0