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Precision gene editing medicine makes history, and it’s just getting started 精密基因编辑医学创造了历史，而这才刚刚开始
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-30 DOI: 10.1038/s41587-025-02741-6
{"title":"Precision gene editing medicine makes history, and it’s just getting started","authors":"","doi":"10.1038/s41587-025-02741-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02741-6","url":null,"abstract":"Despite their astounding success, custom-made base editors and prime editors will need time to broaden their clinical impact.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"33 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520437","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
Improving engineered biological systems with electronics and microfluidics 用电子学和微流体技术改进工程生物系统
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-27 DOI: 10.1038/s41587-025-02709-6
Rabia Tugce Yazicigil, Akshaya Bali, Dilara Caygara, Douglas Densmore
{"title":"Improving engineered biological systems with electronics and microfluidics","authors":"Rabia Tugce Yazicigil, Akshaya Bali, Dilara Caygara, Douglas Densmore","doi":"10.1038/s41587-025-02709-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02709-6","url":null,"abstract":"<p>Hybrid engineered biological systems integrate electronics and microfluidics with engineered biological components, such as microbes or cell-free DNA-based systems, to effectively sense, act upon and report on biological environments. As these engineered biological systems become essential in addressing challenges in healthcare, environmental monitoring, remediation and agriculture, this Review offers an in-depth discussion of their applications, critical design choices and challenges. Alongside an overview of the state of the field, we present a classification framework aimed at helping researchers make informed and optimized design decisions tailored to the intended biological application. Furthermore, we outline how the development of cyber-secure biological systems could enhance the security and functionality of engineered biological platforms. Last, we introduce a ‘Living Roadmap’ (https://www.programmingbiology.org/csbs) to dynamically reflect the field’s progress and support continuous monitoring of future advancements.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"57 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500419","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
Lipid nanoparticle screening in nonhuman primates with minimal loss of life 脂质纳米颗粒筛选非人灵长类动物与最小的生命损失
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-26 DOI: 10.1038/s41587-025-02711-y
Ryan Zenhausern, Bora Jang, Elisa Schrader Echeverri, Kara Gentry, Randi Calkins, Elizabeth H. Curran, Jennifer S. Wood, Rachelle L. Stammen, David Loughrey, Prasanthi Chappa, Dorothy Koveal, Hyejin Kim, James E. Dahlman
{"title":"Lipid nanoparticle screening in nonhuman primates with minimal loss of life","authors":"Ryan Zenhausern, Bora Jang, Elisa Schrader Echeverri, Kara Gentry, Randi Calkins, Elizabeth H. Curran, Jennifer S. Wood, Rachelle L. Stammen, David Loughrey, Prasanthi Chappa, Dorothy Koveal, Hyejin Kim, James E. Dahlman","doi":"10.1038/s41587-025-02711-y","DOIUrl":"https://doi.org/10.1038/s41587-025-02711-y","url":null,"abstract":"<p>Understanding how well delivery in mice predicts delivery in nonhuman primates (NHPs) could make lipid nanoparticle (LNP) discovery more efficient. Yet, few LNP-mRNA drug candidates are tested in NHPs, in part because the experiments require more animals than is considered ethical. Here, to minimize animal use, we create a pool of sterile barcoded LNPs that are frozen, aliquoted and administered when an end-of-life NHP—an animal that is independently scheduled for euthanasia due to spontaneous disease—becomes available. We then administer this pool of 45 LNP-aVHH mRNAs with different chemistries intravenously to mice and NHPs and observe a higher amount of aVHH expression in NHPs than in mice. We characterize systemic physiological responses to LNP treatment using 47 clinically relevant variables and analyze the transcriptomic response alongside delivery in single cells from three tissues in vivo. These data suggest that multiple lipoprotein receptors may be associated with delivery. Altogether, end-of-life NHPs reduce animal use and may be informative preclinical models.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"46 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488402","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 trial of fetal cells for Parkinson’s disease brings lessons for the field 胎儿细胞治疗帕金森病的试验为该领域带来了经验教训
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-26 DOI: 10.1038/s41587-025-02742-5
Viviane Tabar
{"title":"A trial of fetal cells for Parkinson’s disease brings lessons for the field","authors":"Viviane Tabar","doi":"10.1038/s41587-025-02742-5","DOIUrl":"https://doi.org/10.1038/s41587-025-02742-5","url":null,"abstract":"A clinical trial attempts to standardize fetal cell transplantation and highlights challenges to be addressed in upcoming studies that use stem cell-derived neuron progenitors.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"17 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488400","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 editor-based high-throughput screening reveals functional synonymous mutations in human cells 基于Prime编辑器的高通量筛选揭示了人类细胞中的功能同义突变
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-24 DOI: 10.1038/s41587-025-02710-z
Xuran Niu, Wei Tang, Yongshuo Liu, Binrui Mo, Ying Yu, Ying Liu, Wensheng Wei
{"title":"Prime editor-based high-throughput screening reveals functional synonymous mutations in human cells","authors":"Xuran Niu, Wei Tang, Yongshuo Liu, Binrui Mo, Ying Yu, Ying Liu, Wensheng Wei","doi":"10.1038/s41587-025-02710-z","DOIUrl":"https://doi.org/10.1038/s41587-025-02710-z","url":null,"abstract":"<p>Synonymous mutations are generally considered neutral, while their roles in the human genome remain largely unexplored. Here we use the PEmax system to create a library of 297,900 engineered prime-editing guide RNAs and perform extensive screening to identify synonymous mutations affecting cell fitness. Unlike recent findings in yeast, group-level analyses show that synonymous mutations diverge from nonsynonymous mutations in fitness effects yet exhibit similar phenotypic distributions relative to negative controls. Following rigorous quality control, only a small subset demonstrated measurable effects. For these functional mutations, we develop a specialized machine learning tool and uncover their impact on various biological processes such as messenger RNA splicing and transcription, supported by multifaceted experimental evidence. We find that synonymous mutations can alter RNA folding and affect translation, as demonstrated by PLK1_S2. By integrating screening data with our model, we predict clinically deleterious synonymous mutations. This research deepens our understanding of synonymous mutations, providing insights for clinical disease studies.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"29 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371178","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
Identification of non-canonical peptides with moPepGen 用moPepGen鉴定非规范肽
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02701-0
Chenghao Zhu, Lydia Y. Liu, Annie Ha, Takafumi N. Yamaguchi, Helen Zhu, Rupert Hugh-White, Julie Livingstone, Yash Patel, Thomas Kislinger, Paul C. Boutros
{"title":"Identification of non-canonical peptides with moPepGen","authors":"Chenghao Zhu, Lydia Y. Liu, Annie Ha, Takafumi N. Yamaguchi, Helen Zhu, Rupert Hugh-White, Julie Livingstone, Yash Patel, Thomas Kislinger, Paul C. Boutros","doi":"10.1038/s41587-025-02701-0","DOIUrl":"https://doi.org/10.1038/s41587-025-02701-0","url":null,"abstract":"<p>Proteogenomics is limited by the challenge of modeling the complexities of gene expression. We create moPepGen, a graph-based algorithm that comprehensively generates non-canonical peptides in linear time. moPepGen works with multiple technologies, in multiple species and on all types of genetic and transcriptomic data. In human cancer proteomes, it enumerates previously unobservable noncanonical peptides arising from germline and somatic genomic variants, noncoding open reading frames, RNA fusions and RNA circularization.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"272 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296162","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 laboratory-evolved CRISPR-associated transposase adapts to human cells 实验室进化的crispr相关转座酶适应于人类细胞
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02720-x
Iris Marchal
{"title":"A laboratory-evolved CRISPR-associated transposase adapts to human cells","authors":"Iris Marchal","doi":"10.1038/s41587-025-02720-x","DOIUrl":"https://doi.org/10.1038/s41587-025-02720-x","url":null,"abstract":"<p>CRISPR-associated transposases (CASTs) are an attractive candidate for genome editing applications, as they enable the insertion of large DNA cargoes without creating double-strand breaks. However, CAST systems have shown limited activity in human cells. In a paper published in <i>Science</i>, Witte et al. apply phage-assisted continuous evolution (PACE) to direct the rapid evolution of new CAST variants, acquiring a CAST system capable of efficiently integrating gene-size cargoes in human cells.</p><p>Iterative rounds of PACE yielded an evolved TnsB — a component of the Type I-F CAST transposition machinery — with integration efficiency in HEK cells more than 200-fold higher than that of the wild type. The evolved TnsB contained ten activity-enhancing mutations spanning multiple domains, suggesting that PACE optimized diverse functionalities to improve TnsB’s performance and that obtaining such a variant through rational protein engineering would have been unlikely. Notably, the evolved TnsB did not require supplementation with the accessory protein ClpX, a cytotoxic factor previously used to increase CAST editing efficiency.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"178 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304785","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
Court reignites CRISPR patent dispute 法院重新点燃CRISPR专利之争
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02717-6
{"title":"Court reignites CRISPR patent dispute","authors":"","doi":"10.1038/s41587-025-02717-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02717-6","url":null,"abstract":"<p>The University of California and the University of Vienna have convinced a US appeals court to revive their bid for patent rights to the CRISPR–Cas9 gene-editing technology created by their scientists Jennifer Doudna and Emmanuelle Charpentier. The case was sent back to the Patent Office’s Patent Trial and Appeal Board for reconsideration after the court found fault with a previous patent tribunal’s ruling giving key CRISPR–Cas9 patent rights to the Broad Institute and researcher Feng Zhang. This will give Nobel prize winners Doudna and Charpentier and their respective universities another chance to claim rights to CRISPR–Cas9 patents as true inventors in the United States.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"13 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304790","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 New Clinical Investigation exclusivity: a substantial source of monopoly time for brand drugs 新的临床研究排他性：品牌药垄断时间的实质性来源
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02696-8
Robin Feldman, Gideon Schor, Ramy Alsaffar
{"title":"The New Clinical Investigation exclusivity: a substantial source of monopoly time for brand drugs","authors":"Robin Feldman, Gideon Schor, Ramy Alsaffar","doi":"10.1038/s41587-025-02696-8","DOIUrl":"https://doi.org/10.1038/s41587-025-02696-8","url":null,"abstract":"In the United States, some non-patent exclusivities can have an outsized impact on the ability of generic competitors to enter the market and lower drug prices.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"153 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304607","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
CRISPR-TO directs RNA to defined intracellular locations CRISPR-TO将RNA引导到细胞内的特定位置
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02721-w
Iris Marchal
{"title":"CRISPR-TO directs RNA to defined intracellular locations","authors":"Iris Marchal","doi":"10.1038/s41587-025-02721-w","DOIUrl":"https://doi.org/10.1038/s41587-025-02721-w","url":null,"abstract":"<p>Although spatial RNA organization is central to cellular functions and disease mechanisms, its functional consequences remain poorly understood owing to a lack of tools for manipulating RNA localization within cells. Writing in <i>Nature</i>, Han et al. introduce CRISPR-mediated transcriptome organization (CRISPR-TO), a method that uses the RNA-guiding properties of nuclease-dead dCas13 to transport endogenous RNA to desired subcellular compartments. CRISPR-TO works via chemical-inducible dimerization and consists of three components: a dCas13 fused with one dimerization domain, a subcellular localization signal or motor protein fused with the other dimerization domain, and guide RNAs targeting the RNA of interest. The plant hormone ABA was selected as the inducer.</p><p>The authors tested CRISPR-TO by localizing various endogenous mRNAs to the outer mitochondrial membrane (OMM). They observed substantial OMM localization of the target mRNAs despite their varying expression levels. The use of three dCas13-binding sites on a target mRNA yielded 50.6% localization to the OMM.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"88 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304786","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
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