Pub Date : 2024-08-14DOI: 10.1038/s41587-024-02365-2
Iris Marchal
{"title":"Bridge RNAs direct programmable DNA rearrangements","authors":"Iris Marchal","doi":"10.1038/s41587-024-02365-2","DOIUrl":"10.1038/s41587-024-02365-2","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1182-1182"},"PeriodicalIF":33.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982830","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}
Pub Date : 2024-08-14DOI: 10.1038/s41587-024-02364-3
Iris Marchal
{"title":"Joint profiling of drug–chromatin binding and epigenetic landscapes in single cells","authors":"Iris Marchal","doi":"10.1038/s41587-024-02364-3","DOIUrl":"10.1038/s41587-024-02364-3","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1182-1182"},"PeriodicalIF":33.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982834","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}
Pub Date : 2024-08-14DOI: 10.1038/s41587-024-02351-8
Mabel Andalón, Catherine de Fontenay, Donna K. Ginther, Kwanghui Lim
The rise in team size in academic science has generated an unintended side effect: junior scientists are less likely to secure research funding or obtain tenure and are more likely to leave academia.
{"title":"The rise of teamwork and career prospects in academic science","authors":"Mabel Andalón, Catherine de Fontenay, Donna K. Ginther, Kwanghui Lim","doi":"10.1038/s41587-024-02351-8","DOIUrl":"10.1038/s41587-024-02351-8","url":null,"abstract":"The rise in team size in academic science has generated an unintended side effect: junior scientists are less likely to secure research funding or obtain tenure and are more likely to leave academia.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1314-1319"},"PeriodicalIF":33.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982839","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}
Pub Date : 2024-08-14DOI: 10.1038/s41587-024-02310-3
{"title":"From Bench to Podcast: Sean Johnson","authors":"","doi":"10.1038/s41587-024-02310-3","DOIUrl":"10.1038/s41587-024-02310-3","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1189-1189"},"PeriodicalIF":33.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982831","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}
Pub Date : 2024-08-12DOI: 10.1038/s41587-024-02383-0
Nicolas Mathis, Ahmed Allam, András Tálas, Lucas Kissling, Elena Benvenuto, Lukas Schmidheini, Ruben Schep, Tanav Damodharan, Zsolt Balázs, Sharan Janjuha, Eleonora I Ioannidi, Desirée Böck, Bas van Steensel, Michael Krauthammer, Gerald Schwank
{"title":"Publisher Correction: Machine learning prediction of prime editing efficiency across diverse chromatin contexts.","authors":"Nicolas Mathis, Ahmed Allam, András Tálas, Lucas Kissling, Elena Benvenuto, Lukas Schmidheini, Ruben Schep, Tanav Damodharan, Zsolt Balázs, Sharan Janjuha, Eleonora I Ioannidi, Desirée Böck, Bas van Steensel, Michael Krauthammer, Gerald Schwank","doi":"10.1038/s41587-024-02383-0","DOIUrl":"10.1038/s41587-024-02383-0","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":33.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971523","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}
Pub Date : 2024-08-08DOI: 10.1038/s41587-024-02357-2
Melanie Senior
After a difficult three years, biotech financing may slowly be returning to health.
在经历了艰难的三年后，生物技术融资可能正在慢慢恢复健康。
{"title":"Biotech financing: darkest before the dawn","authors":"Melanie Senior","doi":"10.1038/s41587-024-02357-2","DOIUrl":"10.1038/s41587-024-02357-2","url":null,"abstract":"After a difficult three years, biotech financing may slowly be returning to health.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 9","pages":"1331-1338"},"PeriodicalIF":33.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02357-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1038/s41587-024-02373-2
As cultivated meat begins to enter grocery stores, governments should promote the field’s development in line with broad public goals of sustainability and accessibility.
随着栽培肉开始进入杂货店，各国政府应根据可持续发展和可获得性的广泛公共目标，促进该领域的发展。
{"title":"Slaughter-free meat hits the grocery shelf","authors":"","doi":"10.1038/s41587-024-02373-2","DOIUrl":"10.1038/s41587-024-02373-2","url":null,"abstract":"As cultivated meat begins to enter grocery stores, governments should promote the field’s development in line with broad public goals of sustainability and accessibility.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1157-1157"},"PeriodicalIF":33.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02373-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1038/s41587-024-02336-7
Ken Yamada, Vignesh N Hariharan, Jillian Caiazzi, Rachael Miller, Chantal M Ferguson, Ellen Sapp, Hassan H Fakih, Qi Tang, Nozomi Yamada, Raymond C Furgal, Joseph D Paquette, Annabelle Biscans, Brianna M Bramato, Nicholas McHugh, Ashley Summers, Clemens Lochmann, Bruno M D C Godinho, Samuel Hildebrand, Samuel O Jackson, Dimas Echeverria, Matthew R Hassler, Julia F Alterman, Marian DiFiglia, Neil Aronin, Anastasia Khvorova
Therapeutic small interfering RNA (siRNA) requires sugar and backbone modifications to inhibit nuclease degradation. However, metabolic stabilization by phosphorothioate (PS), the only backbone chemistry used clinically, may be insufficient for targeting extrahepatic tissues. To improve oligonucleotide stabilization, we report the discovery, synthesis and characterization of extended nucleic acid (exNA) consisting of a methylene insertion between the 5'-C and 5'-OH of a nucleoside. exNA incorporation is compatible with common oligonucleotide synthetic protocols and the PS backbone, provides stabilization against 3' and 5' exonucleases and is tolerated at multiple oligonucleotide positions. A combined exNA-PS backbone enhances resistance to 3' exonuclease by ~32-fold over the conventional PS backbone and by >1,000-fold over the natural phosphodiester backbone, improving tissue exposure, tissue accumulation and efficacy in mice, both systemically and in the brain. The improved efficacy and durability imparted by exNA may enable therapeutic interventions in extrahepatic tissues, both with siRNA and with other oligonucleotides such as CRISPR guide RNA, antisense oligonucleotides, mRNA and tRNA.
{"title":"Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.","authors":"Ken Yamada, Vignesh N Hariharan, Jillian Caiazzi, Rachael Miller, Chantal M Ferguson, Ellen Sapp, Hassan H Fakih, Qi Tang, Nozomi Yamada, Raymond C Furgal, Joseph D Paquette, Annabelle Biscans, Brianna M Bramato, Nicholas McHugh, Ashley Summers, Clemens Lochmann, Bruno M D C Godinho, Samuel Hildebrand, Samuel O Jackson, Dimas Echeverria, Matthew R Hassler, Julia F Alterman, Marian DiFiglia, Neil Aronin, Anastasia Khvorova","doi":"10.1038/s41587-024-02336-7","DOIUrl":"10.1038/s41587-024-02336-7","url":null,"abstract":"<p><p>Therapeutic small interfering RNA (siRNA) requires sugar and backbone modifications to inhibit nuclease degradation. However, metabolic stabilization by phosphorothioate (PS), the only backbone chemistry used clinically, may be insufficient for targeting extrahepatic tissues. To improve oligonucleotide stabilization, we report the discovery, synthesis and characterization of extended nucleic acid (exNA) consisting of a methylene insertion between the 5'-C and 5'-OH of a nucleoside. exNA incorporation is compatible with common oligonucleotide synthetic protocols and the PS backbone, provides stabilization against 3' and 5' exonucleases and is tolerated at multiple oligonucleotide positions. A combined exNA-PS backbone enhances resistance to 3' exonuclease by ~32-fold over the conventional PS backbone and by >1,000-fold over the natural phosphodiester backbone, improving tissue exposure, tissue accumulation and efficacy in mice, both systemically and in the brain. The improved efficacy and durability imparted by exNA may enable therapeutic interventions in extrahepatic tissues, both with siRNA and with other oligonucleotides such as CRISPR guide RNA, antisense oligonucleotides, mRNA and tRNA.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":33.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875452","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}
Pub Date : 2024-07-29DOI: 10.1038/s41587-024-02320-1
Sean R. McCutcheon, Dahlia Rohm, Nahid Iglesias, Charles A. Gersbach
Epigenome editing has rapidly evolved in recent years, with diverse applications that include elucidating gene regulation mechanisms, annotating coding and noncoding genome functions and programming cell state and lineage specification. Importantly, given the ubiquitous role of epigenetics in complex phenotypes, epigenome editing has unique potential to impact a broad spectrum of diseases. By leveraging powerful DNA-targeting technologies, such as CRISPR, epigenome editing exploits the heritable and reversible mechanisms of epigenetics to alter gene expression without introducing DNA breaks, inducing DNA damage or relying on DNA repair pathways. Epigenome editing has versatile applications in biomedical research and disease treatment.
表观基因组编辑近年来发展迅速，其应用领域多种多样，包括阐明基因调控机制、注释编码和非编码基因组功能以及编程细胞状态和品系规范。重要的是，由于表观遗传学在复杂表型中的作用无处不在，表观基因组编辑具有影响多种疾病的独特潜力。通过利用 CRISPR 等强大的 DNA 靶向技术，表观基因组编辑利用了表观遗传学的可遗传和可逆机制来改变基因表达，而无需引入 DNA 断裂、诱导 DNA 损伤或依赖 DNA 修复途径。
{"title":"Epigenome editing technologies for discovery and medicine","authors":"Sean R. McCutcheon, Dahlia Rohm, Nahid Iglesias, Charles A. Gersbach","doi":"10.1038/s41587-024-02320-1","DOIUrl":"10.1038/s41587-024-02320-1","url":null,"abstract":"Epigenome editing has rapidly evolved in recent years, with diverse applications that include elucidating gene regulation mechanisms, annotating coding and noncoding genome functions and programming cell state and lineage specification. Importantly, given the ubiquitous role of epigenetics in complex phenotypes, epigenome editing has unique potential to impact a broad spectrum of diseases. By leveraging powerful DNA-targeting technologies, such as CRISPR, epigenome editing exploits the heritable and reversible mechanisms of epigenetics to alter gene expression without introducing DNA breaks, inducing DNA damage or relying on DNA repair pathways. Epigenome editing has versatile applications in biomedical research and disease treatment.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1199-1217"},"PeriodicalIF":33.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790968","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}
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