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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
{"title":"Pooled CRISPR screens with joint single-nucleus chromatin accessibility and transcriptome profiling","authors":"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","doi":"10.1038/s41587-024-02475-x","DOIUrl":"https://doi.org/10.1038/s41587-024-02475-x","url":null,"abstract":"<p>Pooled single-cell CRISPR screens have profiled either gene expression or chromatin accessibility but not both modalities. Here we develop MultiPerturb-seq, a high-throughput CRISPR screening platform with joint single-nucleus chromatin accessibility, transcriptome and guide RNA capture using combinatorial indexing combined with droplet microfluidics to scale throughput and integrate all three modalities. We identify key differentiation genes in a rare pediatric cancer and establish <i>ZNHIT1</i> as a potential target for cancer reprogramming therapy.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"1 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678680","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
Editor’s pick: Gate Bioscience 编辑推荐盖特生物科学公司
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2024-11-20 DOI: 10.1038/s41587-024-02483-x
{"title":"Editor’s pick: Gate Bioscience","authors":"","doi":"10.1038/s41587-024-02483-x","DOIUrl":"https://doi.org/10.1038/s41587-024-02483-x","url":null,"abstract":"Each year, Nature Biotechnology highlights companies that have received sizeable early-stage funding in the previous year. Gate Bioscience wants to tailor gates that stop problematic proteins at the source.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"23 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673781","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
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 46.9 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
{"title":"Author Correction: Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells","authors":"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","doi":"10.1038/s41587-024-02502-x","DOIUrl":"https://doi.org/10.1038/s41587-024-02502-x","url":null,"abstract":"<p>Correction to: <i>Nature Biotechnology</i> https://doi.org/10.1038/s41587-022-01637-z, published online 19 January 2023.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"62 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609984","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
Directed evolution of engineered virus-like particles with improved production and transduction efficiencies 改进生产和转导效率的工程病毒颗粒的定向进化
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2024-11-13 DOI: 10.1038/s41587-024-02467-x
Aditya Raguram, Meirui An, Paul Z. Chen, David R. Liu
{"title":"Directed evolution of engineered virus-like particles with improved production and transduction efficiencies","authors":"Aditya Raguram, Meirui An, Paul Z. Chen, David R. Liu","doi":"10.1038/s41587-024-02467-x","DOIUrl":"https://doi.org/10.1038/s41587-024-02467-x","url":null,"abstract":"<p>Engineered virus-like particles (eVLPs) are promising vehicles for transient delivery of proteins and RNAs, including gene editing agents. We report a system for the laboratory evolution of eVLPs that enables the discovery of eVLP variants with improved properties. The system uses barcoded guide RNAs loaded within DNA-free eVLP-packaged cargos to uniquely label each eVLP variant in a library, enabling the identification of desired variants following selections for desired properties. We applied this system to mutate and select eVLP capsids with improved eVLP production properties or transduction efficiencies in human cells. By combining beneficial capsid mutations, we developed fifth-generation (v5) eVLPs, which exhibit a 2–4-fold increase in cultured mammalian cell delivery potency compared to previous-best v4 eVLPs. Analyses of v5 eVLPs suggest that these capsid mutations optimize packaging and delivery of desired ribonucleoprotein cargos rather than native viral genomes and substantially alter eVLP capsid structure. These findings suggest the potential of barcoded eVLP evolution to support the development of improved eVLPs.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"159 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601077","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
Virus-like elements 病毒样元素
IF 33.1 1区 生物学
Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02452-4
{"title":"Virus-like elements","authors":"","doi":"10.1038/s41587-024-02452-4","DOIUrl":"10.1038/s41587-024-02452-4","url":null,"abstract":"Recent patents relating to retroviruses, transposons and other virus-like elements for use in gene transfer and gene therapy.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1649-1649"},"PeriodicalIF":33.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600851","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
Behind the graduate mental health crisis in science 科学界毕业生心理健康危机的背后
IF 33.1 1区 生物学
Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02457-z
Carly A. Busch, Nicholas J. Wiesenthal, Logan E. Gin, Katelyn M. Cooper
{"title":"Behind the graduate mental health crisis in science","authors":"Carly A. Busch,&nbsp;Nicholas J. Wiesenthal,&nbsp;Logan E. Gin,&nbsp;Katelyn M. Cooper","doi":"10.1038/s41587-024-02457-z","DOIUrl":"10.1038/s41587-024-02457-z","url":null,"abstract":"Survey results identify how scientific research and teaching contribute to the graduate student mental health crisis.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1749-1753"},"PeriodicalIF":33.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600860","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
Saturation profiling of drug-resistant genetic variants using prime editing 利用素材编辑技术对耐药性基因变异进行饱和分析
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02465-z
Younggwang Kim, Hyeong-Cheol Oh, Seungho Lee, Hyongbum Henry Kim
{"title":"Saturation profiling of drug-resistant genetic variants using prime editing","authors":"Younggwang Kim, Hyeong-Cheol Oh, Seungho Lee, Hyongbum Henry Kim","doi":"10.1038/s41587-024-02465-z","DOIUrl":"https://doi.org/10.1038/s41587-024-02465-z","url":null,"abstract":"<p>Methods to characterize the functional effects of genetic variants of uncertain significance (VUSs) have been limited by incomplete coverage of the mutational space. In clinical oncology, drug resistance arising from VUSs can prevent optimal treatment. Here we introduce PEER-seq, a high-throughput method based on prime editing that can evaluate the functional effects of single-nucleotide variants (SNVs). PEER-seq introduces both intended SNVs and synonymous marker mutations using prime editing and deep sequences the endogenous target regions to identify the introduced SNVs. We generate and functionally evaluate 2,476 SNVs in the epidermal growth factor receptor gene (<i>EGFR</i>), including 99% of all possible variants in the canonical tyrosine kinase domain. We determined resistance profiles of 95% of all possible EGFR protein variants encoded in the whole tyrosine kinase domain against the common tyrosine kinase inhibitors afatinib, osimertinib and osimertinib in the presence of the co-occurring substitution T790M, in PC-9 cells. Our study has the potential to substantially improve the precision of therapeutic choices in clinical settings.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"95 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599581","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
First proof-of-mechanism for RNA editing in humans 人类首次证明了 RNA 编辑的机制
IF 33.1 1区 生物学
Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02481-z
{"title":"First proof-of-mechanism for RNA editing in humans","authors":"","doi":"10.1038/s41587-024-02481-z","DOIUrl":"10.1038/s41587-024-02481-z","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1627-1627"},"PeriodicalIF":33.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600869","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
A bacterial neoantigen cancer vaccine 细菌新抗原癌症疫苗
IF 33.1 1区 生物学
Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02479-7
Iris Marchal
{"title":"A bacterial neoantigen cancer vaccine","authors":"Iris Marchal","doi":"10.1038/s41587-024-02479-7","DOIUrl":"10.1038/s41587-024-02479-7","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1650-1650"},"PeriodicalIF":33.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600853","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
Who made the mRNA vaccine? Measuring division of labor in therapeutic innovation 谁制造了 mRNA 疫苗？衡量治疗创新中的分工
IF 33.1 1区 生物学
Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02441-7
Martin Ho, Henry C. W. Price, Tim S. Evans, Eoin O’Sullivan
{"title":"Who made the mRNA vaccine? Measuring division of labor in therapeutic innovation","authors":"Martin Ho,&nbsp;Henry C. W. Price,&nbsp;Tim S. Evans,&nbsp;Eoin O’Sullivan","doi":"10.1038/s41587-024-02441-7","DOIUrl":"10.1038/s41587-024-02441-7","url":null,"abstract":"To accelerate future vaccine development, understanding the longer-term funding dynamics behind recent successes such as the USA’s Operation Warp Speed and the UK’s Vaccine Taskforce is imperative.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 11","pages":"1643-1648"},"PeriodicalIF":33.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600859","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
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