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Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase. 用实验室进化的crispr相关转座酶在人类细胞中插入可编程基因。
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15 DOI: 10.1126/science.adt5199
Isaac P Witte, George D Lampe, Simon Eitzinger, Shannon M Miller, Kiara N Berríos, Amber N McElroy, Rebeca T King, Olivia G Stringham, Diego R Gelsinger, Phuc Leo H Vo, Albert T Chen, Jakub Tolar, Mark J Osborn, Samuel H Sternberg, David R Liu
{"title":"Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase.","authors":"Isaac P Witte, George D Lampe, Simon Eitzinger, Shannon M Miller, Kiara N Berríos, Amber N McElroy, Rebeca T King, Olivia G Stringham, Diego R Gelsinger, Phuc Leo H Vo, Albert T Chen, Jakub Tolar, Mark J Osborn, Samuel H Sternberg, David R Liu","doi":"10.1126/science.adt5199","DOIUrl":"https://doi.org/10.1126/science.adt5199","url":null,"abstract":"<p><p>Programmable gene integration in human cells has the potential to enable mutation-agnostic treatments for loss-of-function genetic diseases and facilitate many applications in the life sciences. CRISPR-associated transposases (CASTs) catalyze RNA-guided DNA integration but thus far demonstrate minimal activity in human cells. Using phage-assisted continuous evolution (PACE), we generated CAST variants with >200-fold average improved integration activity. The evolved CAST system (evoCAST) achieves ~10 to 30% integration efficiencies of kilobase-size DNA cargoes in human cells across 14 tested genomic target sites, including safe harbor loci, sites used for immunotherapy, and genes implicated in loss-of-function diseases, with undetected indels and low levels of off-target integration. Collectively, our findings establish a platform for the laboratory evolution of CASTs and advance a versatile system for programmable gene integration in living systems.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"eadt5199"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Revolutionize textile recycling. 彻底改变纺织品回收。
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15 DOI: 10.1126/science.adw0473
Leilei Dai, Roger Ruan, Hanwu Lei, Rui Xiao, Huiyan Zhang
{"title":"Revolutionize textile recycling.","authors":"Leilei Dai, Roger Ruan, Hanwu Lei, Rui Xiao, Huiyan Zhang","doi":"10.1126/science.adw0473","DOIUrl":"https://doi.org/10.1126/science.adw0473","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"713-714"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Watching electronic ice melt. 看着电子冰融化。
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15 DOI: 10.1126/science.adx5775
Sandeep Joy, Brian Skinner
{"title":"Watching electronic ice melt.","authors":"Sandeep Joy, Brian Skinner","doi":"10.1126/science.adx5775","DOIUrl":"https://doi.org/10.1126/science.adx5775","url":null,"abstract":"<p><p>An experiment captures images of the transition between liquid and solid states of an electron system.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"702-703"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Other Journals. 在其他期刊。
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15 DOI: 10.1126/science.ady9584
Bianca Lopez, Priscilla N Kelly, Mattia Maroso, Marc S Lavine, Angela Hessler, Jake S Yeston, Peter Stern
{"title":"In Other Journals.","authors":"Bianca Lopez, Priscilla N Kelly, Mattia Maroso, Marc S Lavine, Angela Hessler, Jake S Yeston, Peter Stern","doi":"10.1126/science.ady9584","DOIUrl":"https://doi.org/10.1126/science.ady9584","url":null,"abstract":"<p><p>Editors' selections from the current scientific literature.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"716-717"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leaving synthetic pesticides behind. 不使用合成农药。
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15 DOI: 10.1126/science.adv7806
Nian-Feng Wan, Ben A Woodcock, Christoph Scherber, Kris A G Wyckhuys, Zhong Li, Xuhong Qian
{"title":"Leaving synthetic pesticides behind.","authors":"Nian-Feng Wan, Ben A Woodcock, Christoph Scherber, Kris A G Wyckhuys, Zhong Li, Xuhong Qian","doi":"10.1126/science.adv7806","DOIUrl":"https://doi.org/10.1126/science.adv7806","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"712-713"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mind reader? 读者吗?
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15 DOI: 10.1126/science.ady9585
Jonathan Moens
{"title":"Mind reader?","authors":"Jonathan Moens","doi":"10.1126/science.ady9585","DOIUrl":"https://doi.org/10.1126/science.ady9585","url":null,"abstract":"<p><p>A forensic technology developed in India sifts brain recordings for clues to a suspect's guilt or innocence. Many neuroscientists are skeptical, but it is catching on in other countries.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"694-698"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From North Asia to South America: Tracing the longest human migration through genomic sequencing. 从北亚到南美：通过基因组测序追踪最长的人类迁徙。
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15 DOI: 10.1126/science.adk5081
Elena S Gusareva, Amit Gourav Ghosh, Vladimir N Kharkov, Seik-Soon Khor, Aleksei Zarubin, Nikita Moshkov, Namrata Kalsi, Aakrosh Ratan, Cassie E Heinle, Niall Cooke, Claudio M Bravi, Marina V Smolnikova, Sergey Yu Tereshchenko, Eduard W Kasparov, Irina Khitrinskaya, Andrey Marusin, Magomed O Razhabov, Maria V Golubenko, Maria Swarovskaya, Nikita A Kolesnikov, Ksenia V Vagaitseva, Elena R Eremina, Aitalina Sukhomyasova, Olga Shtygasheva, Deepa Panicker, Poh Nee Ang, Choou Fook Lee, Yanqing Koh, See Ting Leong, Changsook Park, Sachin R Lohar, Zhei Hwee Yap, Soo Guek Ng, Justine Dacanay, Daniela I Drautz-Moses, Nurul Adilah Binte Ramli, Katsushi Tokunaga, Ian McGonigle, Inaho Danjoh, Andrés Moreno-Estrada, Atsushi Tajima, Hideyuki Tanabe, Yukio Nakamura, Shigeki Nakagome, Tatiana V Tatarinova, Vadim A Stepanov, Stephan C Schuster, Hie Lim Kim
{"title":"From North Asia to South America: Tracing the longest human migration through genomic sequencing.","authors":"Elena S Gusareva, Amit Gourav Ghosh, Vladimir N Kharkov, Seik-Soon Khor, Aleksei Zarubin, Nikita Moshkov, Namrata Kalsi, Aakrosh Ratan, Cassie E Heinle, Niall Cooke, Claudio M Bravi, Marina V Smolnikova, Sergey Yu Tereshchenko, Eduard W Kasparov, Irina Khitrinskaya, Andrey Marusin, Magomed O Razhabov, Maria V Golubenko, Maria Swarovskaya, Nikita A Kolesnikov, Ksenia V Vagaitseva, Elena R Eremina, Aitalina Sukhomyasova, Olga Shtygasheva, Deepa Panicker, Poh Nee Ang, Choou Fook Lee, Yanqing Koh, See Ting Leong, Changsook Park, Sachin R Lohar, Zhei Hwee Yap, Soo Guek Ng, Justine Dacanay, Daniela I Drautz-Moses, Nurul Adilah Binte Ramli, Katsushi Tokunaga, Ian McGonigle, Inaho Danjoh, Andrés Moreno-Estrada, Atsushi Tajima, Hideyuki Tanabe, Yukio Nakamura, Shigeki Nakagome, Tatiana V Tatarinova, Vadim A Stepanov, Stephan C Schuster, Hie Lim Kim","doi":"10.1126/science.adk5081","DOIUrl":"https://doi.org/10.1126/science.adk5081","url":null,"abstract":"<p><p>Genome sequencing of 1537 individuals from 139 ethnic groups reveals the genetic characteristics of understudied populations in North Asia and South America. Our analysis demonstrates that West Siberian ancestry, represented by the Kets and Nenets, contributed to the genetic ancestry of most Siberian populations. West Beringians, including the Koryaks, Inuit, and Luoravetlans, exhibit genetic adaptation to Arctic climate, including medically relevant variants. In South America, early migrants split into four groups-Amazonians, Andeans, Chaco Amerindians, and Patagonians-~13,900 years ago. Their longest migration led to population decline, whereas settlement in South America's diverse environments caused instant spatial isolation, reducing genetic and immunogenic diversity. These findings highlight how population history and environmental pressures shaped the genetic architecture of human populations across North Asia and South America.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"eadk5081"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Limited evidence for range shift–driven extinction in mountain biota 山地生物群因范围移动而灭绝的证据有限
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15
Yi-Hsiu Chen, Jonathan Lenoir, I-Ching Chen
{"title":"Limited evidence for range shift–driven extinction in mountain biota","authors":"Yi-Hsiu Chen,&nbsp;Jonathan Lenoir,&nbsp;I-Ching Chen","doi":"","DOIUrl":"","url":null,"abstract":"<div >Mountain biodiversity reorganizes rapidly as species shift upslope to track temperatures. Pervasive species redistribution poses substantial threats to mountain ecosystems, a phenomenon sometimes described as an “escalator to extinction,” primarily through mountaintop extinctions, range shift gaps (i.e., rapid shifts of suitable temperatures getting ahead of narrow-range species’ upper limits), and lowland biodiversity attrition, yet empirical evidence remains scarce. In this study, our analysis of 8800 records of historical and modern elevational range limits for 440 animal and 1629 plant species revealed little evidence supporting the proposed threats. Observed changes largely fell within random expectations, accounting for geometric constraints. Although delayed mountaintop extinctions point to accumulating extinction debt, concurrent range expansions of both narrow-range and lowland species suggest thermal niche underfilling, processes that collectively drive biotic homogenization across biologically complex mountain ecosystems.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Astrocytes, hidden puppet masters of the brain 星形胶质细胞，隐藏的大脑傀儡主人
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15
Cagla Eroglu
{"title":"Astrocytes, hidden puppet masters of the brain","authors":"Cagla Eroglu","doi":"","DOIUrl":"","url":null,"abstract":"<div >It is accepted that neuromodulators such as norepinephrine and dopamine bind to and activate receptors on neurons to influence the activity of neuronal circuits and plasticity (changes in strength or wiring patterns) of synaptic connections, thus shaping the behavior of the organism. Unlike classical neurotransmitters (e.g., glutamate), which typically mediate fast, point-to-point synaptic communication, neuromodulators diffuse broadly through neural tissue to regulate the strength, duration, and plasticity of neuronal signaling. Emerging evidence now implicates astrocytes—traditionally seen as passive support cells—as active players in neuromodulation (<i>1</i>–<i>3</i>). However, whether astrocytes are necessary intermediaries in neuromodulation or represent regulatory adjuncts to neuronal actions is unclear. On pages 763, 769, and 776 of this issue, Guttenplan <i>et al</i>. (<i>4</i>), Chen <i>et al</i>. (<i>5</i>), and Lefton <i>et al</i>. (<i>6</i>), respectively, address these gaps in knowledge by reporting that astrocytes are indispensable for neuromodulatory signaling across diverse neural circuits, behavioral contexts, and species.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Other Journals 在其他期刊
IF 44.7 1区 综合性期刊
Science Pub Date : 2025-05-15
Bianca Lopez, Priscilla N. Kelly, Mattia Maroso, Marc S. Lavine, Angela Hessler, Jake S. Yeston, Peter Stern
{"title":"In Other Journals","authors":"Bianca Lopez,&nbsp;Priscilla N. Kelly,&nbsp;Mattia Maroso,&nbsp;Marc S. Lavine,&nbsp;Angela Hessler,&nbsp;Jake S. Yeston,&nbsp;Peter Stern","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/science.ady9584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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