Nature biotechnology最新文献_第4页

Engineered platelets as targeted protein degraders and application to breast cancer models

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-12-03 DOI: 10.1038/s41587-024-02494-8

Yu Chen, Samira Pal, Wen Li, Fengyuan Liu, Sichen Yuan, Quanyin Hu

{"title":"Engineered platelets as targeted protein degraders and application to breast cancer models","authors":"Yu Chen, Samira Pal, Wen Li, Fengyuan Liu, Sichen Yuan, Quanyin Hu","doi":"10.1038/s41587-024-02494-8","DOIUrl":"https://doi.org/10.1038/s41587-024-02494-8","url":null,"abstract":"Clinical application of chimeric molecules for targeted protein degradation has been limited by unfavorable drug-like properties and biosafety concerns arising from nonspecific biodistribution after systemic administration. Here we develop a method to engineer platelets for degradation of either intracellular or extracellular proteins of interest (POIs) in vivo by covalently labeling heat shock protein 90 (HSP90) in platelets with a POI ligand. The degrader platelets (DePLTs) target wound areas and undergo activation. Depending on the tethered POI ligand and transport mechanism of the prelabeled HSP90, activated DePLTs can mediate targeted protein degradation in the target cell through the ubiquitin–proteasome machinery or the lysosome. HSP90 packaged into platelet-derived microparticles uses the ubiquitin–proteasome system to degrade intracellular POIs, whereas released free HSP90 redirects extracellular POIs to lysosomal degradation. In postsurgical breast cancer mouse models, DePLTs engineered with corresponding POI ligands effectively degrade intracellular bromodomain-containing protein 4 or extracellular programmed cell death ligand 1, thereby suppressing cancer recurrence or metastasis.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"12 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760379","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

Response to ‘Why Japan lacks a vibrant biotech industry’

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-11-29 DOI: 10.1038/s41587-024-02492-w

Hiroki Ashida, John Stanford

引用次数: 0

Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations 使用 HDR 增强 DNA-PKcs 抑制剂 AZD7648 进行基因组编辑会导致大规模基因组改变

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-27 DOI: 10.1038/s41587-024-02488-6

Grégoire Cullot, Eric J. Aird, Moritz F. Schlapansky, Charles D. Yeh, Lilly van de Venn, Iryna Vykhlyantseva, Susanne Kreutzer, Dominic Mailänder, Bohdan Lewków, Julia Klermund, Christian Montellese, Martina Biserni, Florian Aeschimann, Cédric Vonarburg, Helmuth Gehart, Toni Cathomen, Jacob E. Corn

引用次数: 0

Recovery of biological signals lost in single-cell batch integration with CellANOVA 利用 CellANOVA 恢复单细胞批量整合中丢失的生物信号

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-26 DOI: 10.1038/s41587-024-02463-1

Zhaojun Zhang, Divij Mathew, Tristan L. Lim, Kaishu Mason, Clara Morral Martinez, Sijia Huang, E. John Wherry, Katalin Susztak, Andy J. Minn, Zongming Ma, Nancy R. Zhang

{"title":"Recovery of biological signals lost in single-cell batch integration with CellANOVA","authors":"Zhaojun Zhang, Divij Mathew, Tristan L. Lim, Kaishu Mason, Clara Morral Martinez, Sijia Huang, E. John Wherry, Katalin Susztak, Andy J. Minn, Zongming Ma, Nancy R. Zhang","doi":"10.1038/s41587-024-02463-1","DOIUrl":"https://doi.org/10.1038/s41587-024-02463-1","url":null,"abstract":"Data integration to align cells across batches has become a cornerstone of single-cell data analysis, critically affecting downstream results. Currently, there are no guidelines for when the biological differences between samples are separable from batch effects. Here we show that current paradigms for single-cell data integration remove biologically meaningful variation and introduce distortion. We present a statistical model and computationally scalable algorithm, CellANOVA (cell state space analysis of variance), that harnesses experimental design to explicitly recover biological signals that are erased during single-cell data integration. CellANOVA uses a ‘pool-of-controls’ design concept, applicable across diverse settings, to separate unwanted variation from biological variation of interest and allow the recovery of subtle biological signals. We apply CellANOVA to diverse contexts and validate the recovered biological signals by orthogonal assays. In particular, we show that CellANOVA is effective in the challenging case of single-cell and single-nucleus data integration, where it recovers subtle biological signals that can be validated and replicated by external data.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"191 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713117","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

Intravenous administration of blood–brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system 静脉注射可跨越血脑屏障的共轭物，促进生物大分子向中枢神经系统的转运

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-25 DOI: 10.1038/s41587-024-02487-7

Chang Wang, Siyu Wang, Yonger Xue, Yichen Zhong, Haoyuan Li, Xucheng Hou, Diana D. Kang, Zhengwei Liu, Meng Tian, Leiming Wang, Dinglingge Cao, Yang Yu, Jayce Liu, Xiaolin Cheng, Tamara Markovic, Alice Hashemi, Brian H. Kopell, Alexander W. Charney, Eric J. Nestler, Yizhou Dong

引用次数: 0

Lipid nanoparticle-mediated mRNA delivery to CD34+ cells in rhesus monkeys 脂质纳米颗粒介导的 mRNA 在恒河猴 CD34+ 细胞中的传递

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-22 DOI: 10.1038/s41587-024-02470-2

Hyejin Kim, Ryan Zenhausern, Kara Gentry, Liming Lian, Sebastian G. Huayamares, Afsane Radmand, David Loughrey, Ananda R. Podilapu, Marine Z. C. Hatit, Huanzhen Ni, Andrea Li, Aram Shajii, Hannah E. Peck, Keyi Han, Xuanwen Hua, Shu Jia, Michele Martinez, Charles Lee, Philip J. Santangelo, Alice Tarantal, James E. Dahlman

{"title":"Lipid nanoparticle-mediated mRNA delivery to CD34+ cells in rhesus monkeys","authors":"Hyejin Kim, Ryan Zenhausern, Kara Gentry, Liming Lian, Sebastian G. Huayamares, Afsane Radmand, David Loughrey, Ananda R. Podilapu, Marine Z. C. Hatit, Huanzhen Ni, Andrea Li, Aram Shajii, Hannah E. Peck, Keyi Han, Xuanwen Hua, Shu Jia, Michele Martinez, Charles Lee, Philip J. Santangelo, Alice Tarantal, James E. Dahlman","doi":"10.1038/s41587-024-02470-2","DOIUrl":"https://doi.org/10.1038/s41587-024-02470-2","url":null,"abstract":"Transplantation of ex vivo engineered hematopoietic stem cells (HSCs) can lead to robust clinical responses but carries risks of adverse events from bone marrow mobilization, chemotherapy conditioning and other factors. HSCs have been modified in vivo using lipid nanoparticles (LNPs) decorated with targeting moieties, which increases manufacturing complexity. Here we screen 105 LNPs without targeting ligands for effective homing to the bone marrow in mouse. We report an LNP named LNP67 that delivers mRNA to murine HSCs in vivo, primary human HSCs ex vivo and CD34+ cells in rhesus monkeys (Macaca mulatta) in vivo at doses of 0.25 and 0.4 mg kg−1. Without mobilization and conditioning, LNP67 can mediate delivery of mRNA to HSCs and their progenitor cells (HSPCs), as well as to the liver in rhesus monkeys, without serum cytokine activation. These data support the hypothesis that in vivo delivery to HSCs and HSPCs in nonhuman primates is feasible without targeting ligands.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"16 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684310","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

Pooled CRISPR screens with joint single-nucleus chromatin accessibility and transcriptome profiling 联合单核染色质可及性和转录组图谱的集合 CRISPR 筛选

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-21 DOI: 10.1038/s41587-024-02475-x

Rachel E. Yan, Alba Corman, Lyla Katgara, Xiao Wang, Xinhe Xue, Zoran Z. Gajic, Richard Sam, Michael Farid, Samuel M. Friedman, Jungwook Choo, Ivan Raimondi, Shridar Ganesan, Eugene Katsevich, Jeffrey P. Greenfield, Nadia Dahmane, Neville E. Sanjana

引用次数: 0

Lab-grown breast milk 实验室培育的母乳

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-11-21 DOI: 10.1038/s41587-024-02498-4

Claire Turrell

引用次数: 0

Editor’s pick: Gate Bioscience 编辑推荐盖特生物科学公司

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-11-20 DOI: 10.1038/s41587-024-02483-x

Vivien Marx

引用次数: 0

Author Correction: Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells 作者更正：用嵌合型自身抗体受体T细胞精确靶向肌肉特异性酪氨酸激酶性肌萎缩症的自身抗原特异性B细胞

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-11-14 DOI: 10.1038/s41587-024-02502-x

Sangwook Oh, Xuming Mao, Silvio Manfredo-Vieira, Jinmin Lee, Darshil Patel, Eun Jung Choi, Andrea Alvarado, Ebony Cottman-Thomas, Damian Maseda, Patricia Y. Tsao, Christoph T. Ellebrecht, Sami L. Khella, David P. Richman, Kevin C. O’Connor, Uri Herzberg, Gwendolyn K. Binder, Michael C. Milone, Samik Basu, Aimee S. Payne

引用次数: 0