Nature biotechnology最新文献

{"title":"Leveraging machine learning and big data techniques to map the global patent landscape of phage therapy","authors":"Maxime Descartes Mbogning Fonkou, Jude Dzevela Kong","doi":"10.1038/s41587-024-02493-9","DOIUrl":"10.1038/s41587-024-02493-9","url":null,"abstract":"A patent analysis of the phage therapy field underscores a dynamic, evolving landscape marked by regional disparities and a shift in research focus towards broad-spectrum medical applications and treatments for bacterial infections.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1781-1791"},"PeriodicalIF":33.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02493-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809379","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}

{"title":"Using artificial intelligence to develop gene therapy for the lungs","authors":"","doi":"10.1038/s41587-024-02491-x","DOIUrl":"https://doi.org/10.1038/s41587-024-02491-x","url":null,"abstract":"Gene therapy in the lungs could treat a range of devastating illnesses, but lack of safe and efficient delivery has held back the field. Here, in silico screening of millions of lipid nanoparticles (LNPs) yielded several chemically novel and highly potent LNPs for pulmonary gene therapy.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"19 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809377","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}

{"title":"Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor","authors":"Yanyun Fu, Xiao Ding, Man Zhang, Chunlei Feng, Ziqi Yan, Feng Wang, Jianyu Xu, Xiaoxia Lin, Xiaoyu Ding, Ling Wang, Yaya Fan, Taotao Li, Yushu Yin, Xing Liang, Chenxi Xu, Shan Chen, Fadi E. Pulous, David Gennert, Frank W. Pun, Petrina Kamya, Feng Ren, Alex Aliper, Alex Zhavoronkov","doi":"10.1038/s41587-024-02503-w","DOIUrl":"https://doi.org/10.1038/s41587-024-02503-w","url":null,"abstract":"<p>Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"77 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805097","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}

{"title":"Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy","authors":"Jacob Witten, Idris Raji, Rajith S. Manan, Emily Beyer, Sandra Bartlett, Yinghua Tang, Mehrnoosh Ebadi, Junying Lei, Dien Nguyen, Favour Oladimeji, Allen Yujie Jiang, Elise MacDonald, Yizong Hu, Haseeb Mughal, Ava Self, Evan Collins, Ziying Yan, John F. Engelhardt, Robert Langer, Daniel G. Anderson","doi":"10.1038/s41587-024-02490-y","DOIUrl":"https://doi.org/10.1038/s41587-024-02490-y","url":null,"abstract":"<p>Ionizable lipids are a key component of lipid nanoparticles, the leading nonviral messenger RNA delivery technology. Here, to advance the identification of ionizable lipids beyond current methods, which rely on experimental screening and/or rational design, we introduce lipid optimization using neural networks, a deep-learning strategy for ionizable lipid design. We created a dataset of &gt;9,000 lipid nanoparticle activity measurements and used it to train a directed message-passing neural network for prediction of nucleic acid delivery with diverse lipid structures. Lipid optimization using neural networks predicted RNA delivery in vitro and in vivo and extrapolated to structures divergent from the training set. We evaluated 1.6 million lipids in silico and identified two structures, FO-32 and FO-35, with local mRNA delivery to the mouse muscle and nasal mucosa. FO-32 matched the state of the art for nebulized mRNA delivery to the mouse lung, and both FO-32 and FO-35 efficiently delivered mRNA to ferret lungs. Overall, this work shows the utility of deep learning for improving nanoparticle delivery.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"140 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797068","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}

{"title":"Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells","authors":"Esha Madan, António M. Palma, Vignesh Vudatha, Amit Kumar, Praveen Bhoopathi, Jochen Wilhelm, Tytus Bernas, Patrick C. Martin, Gaurav Bilolikar, Aenya Gogna, Maria Leonor Peixoto, Isabelle Dreier, Thais Fenz Araujo, Elena Garre, Anna Gustafsson, Kalpana Deepa Priya Dorayappan, Narsimha Mamidi, Zhaoyu Sun, Michail Yekelchyk, Davide Accardi, Amalie Lykke Olsen, Lin Lin, Asaf Ashkenazy Titelman, Michael Bianchi, Phil Jessmon, Elnaz Abbasi Farid, Anjan K. Pradhan, Lena Neufeld, Eilam Yeini, Santanu Maji, Christopher J. Pelham, Hyobin Kim, Daniel Oh, Hans Olav Rolfsnes, Rita C. Marques, Amy Lu, Masaki Nagane, Sahil Chaudhary, Kartik Gupta, Keshav C. Gogna, Ana Bigio, Karthikeya Bhoopathi, Padmanabhan Mannangatti, K. Gopinath Achary, Javed Akhtar, Sara Belião, Swadesh Das, Isabel Correia, Cláudia L. da Silva, Arsénio M. Fialho, Michael J. Poellmann, Kaila Javius-Jones, Adam M. Hawkridge, Sanya Pal, Kumari S. Shree, Emad A. Rakha, Sambhav Khurana, Gaoping Xiao, Dongyu Zhang, Arjun Rijal, Charles Lyons, Steven R. Grossman, David P. Turner, Raghavendra Pillappa, Karanvir Prakash, Gaurav Gupta, Gary L. W. G. Robinson, Jennifer Koblinski, Hongjun Wang, Gita Singh, Sujay Singh, Sagar Rayamajhi, Manny D. Bacolod, Hope Richards, Sadia Sayeed, Katherine P. Klein, David Chelmow, Ronit Satchi-Fainaro, Karuppaiyah Selvendiran, Denise Connolly, Frits Alan Thorsen, Rolf Bjerkvig, Kenneth P. Nephew, Michael O. Idowu, Mark P. Kühnel, Christopher Moskaluk, Seungpyo Hong, William L. Redmond, Göran Landberg, Antonio Lopez-Beltran, Andrew S. Poklepovic, Arun Sanyal, Paul B. Fisher, George M. Church, Usha Menon, Ronny Drapkin, Andrew K. Godwin, Yonglun Luo, Maximilian Ackermann, Alexandar Tzankov, Kirsten D. Mertz, Danny Jonigk, Allan Tsung, David Sidransky, Jose Trevino, Arturo P. Saavedra, Robert Winn, Kyoung Jae Won, Eduardo Moreno, Rajan Gogna","doi":"10.1038/s41587-024-02453-3","DOIUrl":"https://doi.org/10.1038/s41587-024-02453-3","url":null,"abstract":"<p>Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, <i>Tu-Stroma</i>, which controls the splicing of the <i>Flower</i> gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"35 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793569","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}

{"title":"Challenges for developing broad-based mucosal vaccines for respiratory viruses","authors":"Junghwa Seo,&nbsp;Jordan Polster,&nbsp;Benjamin Israelow,&nbsp;Kizzmekia S. Corbett-Helaire,&nbsp;David R. Martinez","doi":"10.1038/s41587-024-02486-8","DOIUrl":"10.1038/s41587-024-02486-8","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1765-1767"},"PeriodicalIF":33.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782733","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}

{"title":"Biology and applications of CRISPR–Cas12 and transposon-associated homologs","authors":"Wen Y. Wu,&nbsp;Belén Adiego-Pérez,&nbsp;John van der Oost","doi":"10.1038/s41587-024-02485-9","DOIUrl":"10.1038/s41587-024-02485-9","url":null,"abstract":"CRISPR-associated Cas12 proteins are a highly variable collection of nucleic acid-targeting proteins. All Cas12 variants use RNA guides and a single nuclease domain to target complementary DNA or, in rare cases, RNA. The high variability of Cas12 effectors can be explained by a series of independent evolution events from different transposon-associated TnpB-like ancestors. Despite basic structural and functional similarities, this has resulted in unprecedented variation of the Cas12 effector proteins in terms of size, domain composition, guide structure, target identity and interference strategy. In this Review, we compare the unique molecular features of natural and engineered Cas12 and TnpB variants. Furthermore, we provide an overview of established genome editing and diagnostic applications and discuss potential future directions. Natural and engineered Cas12 and TnpB variants offer diverse applications in genome editing and diagnostics.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1807-1821"},"PeriodicalIF":33.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763651","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}

{"title":"Top ten news stories in 2024","authors":"Lisa Melton","doi":"10.1038/s41587-024-02500-z","DOIUrl":"10.1038/s41587-024-02500-z","url":null,"abstract":"From mRNA drugs and the Achilles heel of obesity drugs, to single-cell biology and foundation models for drug discovery, these are some of the big stories most viewed by our readers.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1757-1758"},"PeriodicalIF":33.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02500-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763763","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}

{"title":"2024: research in review","authors":"","doi":"10.1038/s41587-024-02508-5","DOIUrl":"10.1038/s41587-024-02508-5","url":null,"abstract":"Nature Biotechnology editors pick their favorite research articles from 2024.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1755-1756"},"PeriodicalIF":33.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02508-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763652","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}

{"title":"Proteolytic platelets as targeted protein degraders","authors":"","doi":"10.1038/s41587-024-02495-7","DOIUrl":"https://doi.org/10.1038/s41587-024-02495-7","url":null,"abstract":"Proteolytic chimeras constructed from various bioactive modules can degrade either cytoplasmic or extracellular proteins, but their pharmacology faces challenges. Now, a protein degradation platform built with engineered platelets enables the targeted depletion of intracellular and extracellular proteins at hemorrhagic sites, addressing several limitations associated with proteolytic chimeras.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"13 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760083","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}