Nature biotechnology最新文献_第9页

Discovery and design of potent cell surface display elements. 有效的细胞表面显示元件的发现和设计。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-12 DOI: 10.1038/s41587-026-03144-x

Zhenhao Fang, Joshua Saskin, Seok-Hoon Lee, Charles Zou, Shan Xin, Xiaoyu Huang, Xingxin Pan, Chuanpeng Dong, Ardavan Abiri, Yanzhi Feng, Nidhi Sahni, S Stephen Yi, Lei Peng, Sidi Chen

{"title":"Discovery and design of potent cell surface display elements.","authors":"Zhenhao Fang, Joshua Saskin, Seok-Hoon Lee, Charles Zou, Shan Xin, Xiaoyu Huang, Xingxin Pan, Chuanpeng Dong, Ardavan Abiri, Yanzhi Feng, Nidhi Sahni, S Stephen Yi, Lei Peng, Sidi Chen","doi":"10.1038/s41587-026-03144-x","DOIUrl":"10.1038/s41587-026-03144-x","url":null,"abstract":"Cell surface display (CSD) elements are a major class of bioengineering modules, but systematic rules linking CSD sequence to functional potency are lacking. Here we develop DeepSCan, a suite of deep learning and artificial intelligence models to systematically map CSD sequence-function relationships to reliably capture potent elements' conserved features and iteratively design and develop potent de novo CSD modules for mRNA antigen display. We experimentally quantify surface expression across >570 chimeric antigens, derive cell surface translocation strength labels for ~310 CSD elements and compile ~45 independent training datasets. We train three generations of DeepSCan models and evaluate their performance. Guided by these models, we computationally design 3,700 and experimentally validate approximately 120 generative CSDs, identifying 7 generative CSDs that match or exceed the cell surface translocation strength of the most potent naturally occurring CSDs. Enhanced surface displays are validated across multiple cell types and are functional in an antigen-specific CAR-T cytotoxicity assay.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727023","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

Mechanistic machine learning for prediction of prime editing outcomes. 用于预测主要编辑结果的机械机器学习。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-12 DOI: 10.1038/s41587-026-03261-7

Alvin Hsu, Peter J Chen, Angus H Li, Colin F Hemez, Xin D Gao, Markus Terrey, Charlie Nelson, Vijay Selvam, Ana Cristian, Amber N McElroy, Benjamin J Steinbeck, Gandhar K Mahadeshwar, Smriti Pandey, Zachary Barsdale, Paul Z Chen, Alexander A Sousa, Holt A Sakai, Rachel A Silverstein, Ilias Morad, Ryan K Krueger, Max W Shen, Benjamin P Kleinstiver, Cathleen M Lutz, Jakub Tolar, Bruce R Blazar, Mark J Osborn, David R Liu

{"title":"Mechanistic machine learning for prediction of prime editing outcomes.","authors":"Alvin Hsu, Peter J Chen, Angus H Li, Colin F Hemez, Xin D Gao, Markus Terrey, Charlie Nelson, Vijay Selvam, Ana Cristian, Amber N McElroy, Benjamin J Steinbeck, Gandhar K Mahadeshwar, Smriti Pandey, Zachary Barsdale, Paul Z Chen, Alexander A Sousa, Holt A Sakai, Rachel A Silverstein, Ilias Morad, Ryan K Krueger, Max W Shen, Benjamin P Kleinstiver, Cathleen M Lutz, Jakub Tolar, Bruce R Blazar, Mark J Osborn, David R Liu","doi":"10.1038/s41587-026-03261-7","DOIUrl":"10.1038/s41587-026-03261-7","url":null,"abstract":"Prime editing (PE) can make specific local changes to genomic DNA in living systems but its efficient application currently requires extensive optimization of PE guide RNA (pegRNA) sequences. Here we present OptiPrime, a machine learning model of PE efficiency based on current understanding of PE mechanisms. OptiPrime achieves state-of-the-art accuracy on PE efficiency prediction and enables prediction of nicking guide RNA (PE3) and dual pegRNA (twinPE) outcomes. We validate that OptiPrime has learned the determinants of mammalian mismatch repair (MMR) and is well suited for nominating MMR-evasive silent edits that improve PE efficiency. We demonstrate the use of OptiPrime in a variety of prospective therapeutic contexts in primary human and mouse cells. Lastly, we show that OptiPrime can be used to achieve streamlined and efficient in vivo correction of a pathogenic mutation in the brain of a mouse model of KIF1A-associated neurological disorder. We provide a webserver for OptiPrime ( https://optipri.me/ ) as a community resource.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725415","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

Menstrualome aids difficult endometriosis diagnosis 月经量有助于诊断子宫内膜异位症

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-11 DOI: 10.1038/s41587-026-03265-3

Carrie Arnold

引用次数: 0

Killing resistant tumors with a click 点击一下就能杀死耐药肿瘤

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-11 DOI: 10.1038/s41587-026-03275-1

Dario Ummarino

引用次数: 0

People 人

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-11 DOI: 10.1038/s41587-026-03257-3

引用次数: 0

Author Correction: Engineered living glues secrete therapeutic proteins for treatment of inflammatory bowel disease. 作者更正：工程活胶分泌治疗性蛋白用于治疗炎症性肠病。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-11 DOI: 10.1038/s41587-026-03283-1

Changhao Ge, Shanshan Jiang, Xiaomin Dong, Xiaoyu Jiang, Weiliang Zhi, Chenhao Yang, Yunqing Xiang, Chun Chu, Peilang Yang, Qian Zhang, Xin Chen, Yan Liu, Shuqiang Huang, Yifan Liu, Xiaoshan Shi, Jing Lin, Bolin An, Peng Huang, Chao Zhong

引用次数: 0

From cabozantinib to zanzalintinib: obvious chemical modifications as a new frontier in product hopping 从卡博赞替尼到赞扎替尼：明显的化学修饰是产品跳跃的新前沿

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-11 DOI: 10.1038/s41587-026-03242-w

Garth W. Strohbehn, S. Sean Tu, Xiaodong Wang, Mark J. Ratain

引用次数: 0

Tech giants plunge into life sciences 科技巨头投身生命科学

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-08-11 DOI: 10.1038/s41587-026-03271-5

引用次数: 0

The invisible tax of US visa bureaucracy on international scholars 美国签证制度对国际学者的无形税收

IF 44.5 1区生物学