Nature biotechnology最新文献_第5页

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":"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.","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

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

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":"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 (EGFR), 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.","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

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

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

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Beyond the blood: expanding CAR T cell therapy to solid tumors 超越血液：将 CAR T 细胞疗法扩展到实体瘤

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02446-2

Ugur Uslu, Carl H. June

引用次数: 0

Multimodal scanning of genetic variants with base and prime editing 利用碱基和质点编辑对基因变异进行多模式扫描

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02439-1

Olivier Belli, Kyriaki Karava, Rick Farouni, Randall J. Platt

{"title":"Multimodal scanning of genetic variants with base and prime editing","authors":"Olivier Belli, Kyriaki Karava, Rick Farouni, Randall J. Platt","doi":"10.1038/s41587-024-02439-1","DOIUrl":"https://doi.org/10.1038/s41587-024-02439-1","url":null,"abstract":"Mutational scanning connects genetic variants to phenotype, enabling the interrogation of protein functions, interactions and variant pathogenicity. However, current methodologies cannot efficiently engineer customizable sets of diverse genetic variants in endogenous loci across cellular contexts in high throughput. Here, we combine cytosine and adenine base editors and a prime editor to assess the pathogenicity of a broad spectrum of variants in the epithelial growth factor receptor gene (EGFR). Using pooled base editing and prime editing guide RNA libraries, we install tens of thousands of variants spanning the full coding sequence of EGFR in multiple cell lines and assess the role of these variants in tumorigenesis and resistance to tyrosine kinase inhibitors. Our EGFR variant scan identifies important hits, supporting the robustness of the approach and revealing underappreciated routes to EGFR activation and drug response. We anticipate that multimodal precision mutational scanning can be applied broadly to characterize genetic variation in any genetic element of interest at high and single-nucleotide resolution.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"22 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599579","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

People 人

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-11-12 DOI: 10.1038/s41587-024-02464-0

引用次数: 0