Nature biotechnology最新文献_第4页

Accelerated discovery of thermostable mRNA-lipid nanoparticle vaccines using data-efficient AI. 使用数据高效的人工智能加速发现耐热mrna -脂质纳米颗粒疫苗。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-28 DOI: 10.1038/s41587-026-03331-w

Jinbi Tian, Khanh T M Tran, Brett H Pogostin, Olivia Sheridan, Sevinj Mursalova, Amy H Lee, Shuai Liu, Jaya Hamkins, Daniel Antov, Alana L Power, Zane S Dash, Dongsoo Yun, Mina Konaković Luković, Robert S Langer, Ana Jaklenec

{"title":"Accelerated discovery of thermostable mRNA-lipid nanoparticle vaccines using data-efficient AI.","authors":"Jinbi Tian, Khanh T M Tran, Brett H Pogostin, Olivia Sheridan, Sevinj Mursalova, Amy H Lee, Shuai Liu, Jaya Hamkins, Daniel Antov, Alana L Power, Zane S Dash, Dongsoo Yun, Mina Konaković Luković, Robert S Langer, Ana Jaklenec","doi":"10.1038/s41587-026-03331-w","DOIUrl":"https://doi.org/10.1038/s41587-026-03331-w","url":null,"abstract":"The instability of mRNA-lipid nanoparticles (LNPs) necessitates ultra-cold storage, limiting global distribution and their broader application in advanced delivery systems. Solid-state, water-free formulations enhance thermostability and enable integration into emerging delivery modalities such as microneedle patches. Previous efforts to stabilize mRNA-LNPs have been constrained by narrow formulation scope and low-throughput screening methods. Here we introduce Algorithm-Guided Experimental design for lipid Nanoparticle Thermostabilization (AGENT), an artificial intelligence (AI)-driven framework that couples high-throughput experimentation with Bayesian optimization to identify thermostable mRNA-LNP formulations. AGENT extracts maximal information from sparse experimental datasets, enabling efficient formulation optimization in six iterations completed within 1 month. We stabilized mRNA vaccines with two clinically relevant LNPs representative of the Moderna (SM-102-based) and Pfizer-BioNTech (ALC-0315-based) compositions into solid-state formulations that retained 100% bioactivity after storage at 37 °C for more than 2 months. In rodents and non-human primates, thermostable, solid-state vaccine formulations induced antigen-specific immune responses non-inferior to those elicited by intramuscular delivery of freshly prepared soluble vaccines.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075520","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 nanoparticles optimized for large RNA cargo and tissue targeting enhance in vivo genome editing. 脂质纳米颗粒优化的大RNA货物和组织靶向增强体内基因组编辑。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-28 DOI: 10.1038/s41587-026-03298-8

Songtao Dong, Fanglin Gong, Tyler Thomson, Yunshu Cai, Lauren Healy, Rick X Z Lu, Ziyu Zhou, Yue Xu, Jingan Chen, Margarita Savguira, Xianglei Fu, Sijin Luozhong, Muye Zhou, Payton Kirtley, Brandon K Wilder, Bowen Li

{"title":"Lipid nanoparticles optimized for large RNA cargo and tissue targeting enhance in vivo genome editing.","authors":"Songtao Dong, Fanglin Gong, Tyler Thomson, Yunshu Cai, Lauren Healy, Rick X Z Lu, Ziyu Zhou, Yue Xu, Jingan Chen, Margarita Savguira, Xianglei Fu, Sijin Luozhong, Muye Zhou, Payton Kirtley, Brandon K Wilder, Bowen Li","doi":"10.1038/s41587-026-03298-8","DOIUrl":"https://doi.org/10.1038/s41587-026-03298-8","url":null,"abstract":"Although lipid nanoparticles are clinically validated for RNA delivery, their potency often declines as transcript size increases. Here we report a large-cargo-informed lipid discovery strategy that incorporates mRNA size into ionizable lipid screening. A combinatorial library of 384 lipids was screened using a 5.7-kb ABE-NanoLuc reporter mRNA, identifying large-cargo-optimized lipids led by LC-1. Following intravenous, intrathecal and intratracheal administration, LC-1 achieved up to 79% Cas9-mediated knockout in liver and 48% and 27% in brain and lung, up to fourfold higher than LP-01 and ALC-0315, and produced higher ABE-mediated reporter correction across all three routes. LC-1 supported base editing of PCSK9, CFTRR55X and Ube3a-ATS. Mechanistic studies showed that, unlike the benchmarks, LC-1 forms stronger lipid-RNA interactions and retains an ordered, fusogenic inverted-hexagonal structure and pH-responsive membrane disruption as mRNA size increases, rather than becoming disordered. These findings establish cargo size as a key design parameter for ionizable lipid discovery.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075540","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

Photolabile oligonucleotides with topological light gradients enable spatially resolved single-cell transcriptomics and epigenomics 具有拓扑光梯度的光稳定性寡核苷酸使空间分辨单细胞转录组学和表观基因组学成为可能

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2026-09-25 DOI: 10.1038/s41587-026-03328-5

Robert A. Piscopio,Alex Chialastri,Chieh Wang,Mikolaj Godzik,Kellie A. Heom,Weiyue Wang,Lauren J. Li,Neha Saxena,Maxwell Z. Wilson,Siddharth S. Dey

引用次数: 0

The novel transcripts we keep rediscovering 我们不断重新发现的新记录

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-22 DOI: 10.1038/s41587-026-03321-y

Xinchang Zheng, Sonia Garcia-Ruiz, Emil K. Gustavsson, Mina Ryten, Fritz J. Sedlazeck

引用次数: 0

Gene editing using large insertions 使用大量插入进行基因编辑。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-17 DOI: 10.1038/s41587-026-03319-6

Alexandra Despang

引用次数: 0

FDA approves pioneering breast cancer drug that nips resistance in the bud 美国食品和药物管理局批准了一种开拓性的乳腺癌药物，将耐药性扼杀在萌芽状态。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-16 DOI: 10.1038/s41587-026-03333-8

Charlotte Harrison

引用次数: 0

Ensuring safety and accountability in China’s biomedical translation system 确保中国生物医学翻译系统的安全性和问责性。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-15 DOI: 10.1038/s41587-026-03314-x

Jianqiang Wu

引用次数: 0

A versatile nanopore identifies four classes of analytes simultaneously. 多功能纳米孔可同时识别四类分析物。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-15 DOI: 10.1038/s41587-026-03322-x

引用次数: 0

An engineered nanopore identifies saccharides, amino acids, peptides and ribonucleotides. 一个工程纳米孔可以识别糖类、氨基酸、多肽和核糖核苷酸。

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-14 DOI: 10.1038/s41587-026-03308-9

Lang Yao, Zixuan Wang, Jialu Chen, Wen Sun, Kefan Wang, Yunqi Xiao, Hanhan Zhang, Wenzheng Li, Yifan Wang, Lulu Zhao, Xinyi Dai, Lu Qian, Panke Zhang, Shuo Huang

{"title":"An engineered nanopore identifies saccharides, amino acids, peptides and ribonucleotides.","authors":"Lang Yao, Zixuan Wang, Jialu Chen, Wen Sun, Kefan Wang, Yunqi Xiao, Hanhan Zhang, Wenzheng Li, Yifan Wang, Lulu Zhao, Xinyi Dai, Lu Qian, Panke Zhang, Shuo Huang","doi":"10.1038/s41587-026-03308-9","DOIUrl":"10.1038/s41587-026-03308-9","url":null,"abstract":"Simultaneous characterization of proteins, RNAs and glycans with a nanopore remains a substantial challenge. To advance toward this goal, we introduce a multifunctional adaptor, maleimido-C2-formylphenylboronic acid (maleimido-C2-FPBA), into the Mycobacterium smegmatis porin A (MspA) nanopore at the pore constriction site. Here we demonstrate that the engineered nanopore, MspA-FPBA, enables the simultaneous identification of a diverse set of analytes, including 21 proteinogenic amino acids, three post-translationally modified (PTM) amino acids, four canonical nucleoside monophosphates (NMPs), three epigenetically modified NMPs, four monosaccharides and five peptides. Combined with machine learning, this sensor achieves an overall accuracy of 98.7%. Furthermore, it generates predictable event signatures for specific analyte types, enabling the machine learning model to identify analytes without strictly relying on prearchived event features, as demonstrated by the nanopore analysis of yeast cell extract. Lastly, we apply MspA-FPBA for compositional analysis of G2 glycopeptides. Future integration of hydrolase with MspA-FPBA may further improve MspA-FPBA utility as a single system to identify diverse biomolecules.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970342","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

Biomimetic cells for studying T cell mechanotransduction 用于研究T细胞机械转导的仿生细胞

IF 44.5 1区生物学

Nature biotechnology Pub Date : 2026-09-10 DOI: 10.1038/s41587-026-03312-z

Dario Ummarino

引用次数: 0