Frontiers in genome editing最新文献

{"title":"A long journey towards genome editing technologies in plants: a technical and critical review of genome editing technologies.","authors":"Dylan Gallo, Anne-Cécile Meunier, Christophe Périn","doi":"10.3389/fgeed.2025.1663352","DOIUrl":"https://doi.org/10.3389/fgeed.2025.1663352","url":null,"abstract":"<p><p>Advancements in genome editing technologies, notably CRISPR/Cas9, base editing (BE), and prime editing (PE), have revolutionized plant biotechnology, offering unprecedented precision in crop improvement to address the ongoing global warming challenge. This review provides a critical analysis of recent developments in SpCas9-based editing tools, emphasizing enhancements in editing efficiency and specificity and follow the chronological development of editing tools. We explore methodological innovations, including dual pegRNA strategies and site-specific integrases, that have expanded the potential of PE for precise gene insertions. By integrating insights into DNA repair mechanisms and leveraging SpCas9 enhancements, we outline future directions for the application of genome editing in plant breeding.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1663352"},"PeriodicalIF":4.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12643982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Rewriting the script: gene therapy and genome editing for von Willebrand Disease.","authors":"Alastair Barraclough, Isabel Bär, Tirsa van Duijl, Karin Fijnvandraat, Jeroen C J Eikenboom, Frank W G Leebeek, Ruben Bierings, Jan Voorberg, Despoina Trasanidou","doi":"10.3389/fgeed.2025.1719330","DOIUrl":"10.3389/fgeed.2025.1719330","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fgeed.2025.1620438.].</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1719330"},"PeriodicalIF":4.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings of the second annual meeting of GenE-HumDi (COST Action 21113).","authors":"María Ortiz-Bueno, Iris Ramos-Hernández, Luis Algeciras-Jiménez, Nechama Kalter, Juan Roberto Rodríguez-Madoz, Jose Bonafont, Rajeevkumar Raveendran Nair, Oliver Feeney, Laura Torella, Lluis Montoliu, Petros Patsali, Claudio Mussolino, Yonglun Luo, Merita Xhetani, Alessia Cavazza, Ayal Hendel, Karim Benabdellah, Carsten Werner Lederer, Francisco J Molina-Estévez","doi":"10.3389/fgeed.2025.1667329","DOIUrl":"10.3389/fgeed.2025.1667329","url":null,"abstract":"<p><p>Genome editing for the treatment of human disease (GenE-HumDi) is an EU-funded COST Action for the development and consolidation of academic, industrial and healthcare feedback networks aiming to accelerate, foster and harmonize the approval of genome-editing (GE) therapies. GenE-HumDi offers mobility grants, supports educational courses, and hosts conferences and meetings to promote synergistic interactions among and across partners active in the discovery, validation, optimization, manufacturing and clinical application of genomic medicines. Furthermore, it provides young and early career scientists with a supportive and world-class environment to foster networking and international collaborations within the GE field. We compiled the proceedings of the second Annual GenE-HumDi Meeting held in Limassol, Cyprus, in 2024. Over three days, renowned experts from the field updated an audience of over 70 GenE-HumDi members and non-member scientists on the latest discoveries and ongoing projects, discussed the status of the field, and identified GenE-HumDi action priorities to advance research and development for GE medicines. Seven focused discussion groups identified gaps in knowledge, standardization and dissemination for new GE tools, delivery methods, safety monitoring, validation for clinical use, and progress in industrial manufacturing and regulatory issues. Simultaneously, publicity about the event itself contributed to outreach and dissemination of GE for human diseases. Therefore, the conclusions of that meeting, summarized here, serve as a compass toward GE application in Europe through coordination, enhanced collaboration and focus on critical developments.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1667329"},"PeriodicalIF":4.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12620488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Genome editing for climate change adaptation in agriculture: innovations, applications, and regulatory considerations.","authors":"Koppolu Raja Rajesh Kumar, Prashant Kumar Singh","doi":"10.3389/fgeed.2025.1711767","DOIUrl":"10.3389/fgeed.2025.1711767","url":null,"abstract":"","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1711767"},"PeriodicalIF":4.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12580342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome editing approaches to harness cytokinin-salicylic acid crosstalk for plant protection.","authors":"Muhammad Naseem, Khalid Muhammad","doi":"10.3389/fgeed.2025.1687599","DOIUrl":"10.3389/fgeed.2025.1687599","url":null,"abstract":"","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1687599"},"PeriodicalIF":4.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12580181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9- and Cas3-mediated modification of copy number variation in rice.","authors":"Hyungjun Park, Takeshi Kuroha, Hiroaki Saika, Masaharu Kuroda, Hitoshi Yoshida","doi":"10.3389/fgeed.2025.1652950","DOIUrl":"10.3389/fgeed.2025.1652950","url":null,"abstract":"<p><strong>Introduction: </strong>Copy number variation (CNV) is one of the crucial elements among genomic structural variations that span plant breeding. However, its impact on agricultural traits has remained elusive.</p><p><strong>Methods: </strong>We modulated CNVs using two genome-editing technologies, CRISPR/Cas9 and Cas3, along with their verification methods in rice to elucidate the effect of CNVs and further harness to improve relevant agronomic traits.</p><p><strong>Results: </strong>The addition of cytosine extension to the conventional single-guide RNA and its combination with Cas9 generated a frameshift mutation in parts of the <i>OsGA20ox1</i> gene copies, substantially modifying its CNV. Phenotypes of the copy number variants revealed <i>OsGA20ox1</i> copy number as a determinant of seedling vigor in rice. The Cas3 nuclease, which induces large-scale deletions, effectively decreased the copy number of the <i>OsMTD1</i> gene. We verified the copy number of each gene by combining droplet digital polymerase chain reaction (ddPCR), Sanger sequencing, and bioinformatics tools.</p><p><strong>Discussion: </strong>Altogether, the two technologies are expected to lay the foundation for new approaches to plant breeding by controlling CNV.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1652950"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From GWAS signal to function: targeted CRISPR activation enables functional characterization of non-coding SNPs in chickens.","authors":"Jaewon Kim, Jeong Hoon Han, Minjun Kim, Grace Schmidt, Eunjin Cho, Jun Heon Lee, Tae Hyun Kim","doi":"10.3389/fgeed.2025.1662152","DOIUrl":"10.3389/fgeed.2025.1662152","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with complex traits in poultry. However, most GWAS-identified variants reside in non-coding regions, making their functional relevance to their phenotypes unclear. Emerging evidence suggests that many of these markers overlap <i>cis</i>-regulatory elements, yet experimental validation of their biological function remains limited. Here, we investigated non-coding GWAS variants associated with nucleotide-related compounds in chicken breast muscle by targeting SNP-containing genomic regions using a CRISPR activation (CRISPRa) system in DF-1 cells and profiling transcriptomic responses via bulk RNA sequencing to assess the functional impact of activating these regions. Based on chicken muscle-specific epigenetic profiles and chromatin state annotations, we identified three significant GWAS variants on chromosome five associated with nucleotide metabolism. These variants are situated within <i>cis</i>-regulatory elements, specifically in intron three of <i>DUSP8</i>, intron one of <i>SLC25A22</i>, and upstream of <i>FBXO3</i>. To understand their functional impact, we employed an <i>in vitro</i> CRISPRa system with targeted guide RNAs to activate each non-coding SNP region in DF-1 cells. This activation resulted in significant changes at the transcriptomic level. Subsequent functional enrichment analysis of the differentially expressed genes consistently highlighted muscle-related pathways across all SNPs, including MAPK signaling, cytoskeletal remodeling, and ECM-receptor interactions, which are potentially involved in regulating nucleotide metabolism and deposition in muscle. Furthermore, transcript-level analysis of RNA-seq reads revealed that the non-coding SNP region within the intron three of <i>DUSP8</i> may function as an alternative promoter, resulting in significantly higher expression of a shorter transcript that could generate a non-canonical protein isoform. Our study demonstrates that activating genomic regions harboring specific non-coding GWAS SNPs can modulate gene expression, suggesting that these SNPs may contribute to gene regulatory functions. Importantly, this work underscores the powerful utility of CRISPRa as a functional genomics tool for linking GWAS signals to their biological roles in chickens by targeting SNP-containing regions and uncovering consequential molecular phenotypes.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1662152"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-mediated generation of a tumor-associated antigen-deficient Raji platform to investigate antigen loss in CAR-T cell therapy.","authors":"Aditya Ramdas Iyer, Mehwish Nafiz, Pragya Gupta, Arvinden Vr, Vinodh Saravanakumar, Mohammad Sufyan Ansari, Md Shakir, Tanveer Ahmad, Sivaprakash Ramalingam","doi":"10.3389/fgeed.2025.1649993","DOIUrl":"10.3389/fgeed.2025.1649993","url":null,"abstract":"<p><p>Tumor-associated antigen (TAA) loss remains a significant mechanism of resistance to chimeric antigen receptor (CAR) T cell therapy, leading to relapse in patients with B-cell malignancies and representing a major clinical challenge. Recent clinical data suggest that CD19 antigen loss triggers relapse in more than 40% of patients undergoing CD19 CAR-T cell therapy. To rigorously validate antigen loss, robust <i>in vitro</i> models that mimic the dynamic process of antigen escape are essential. However, the current absence of these models hampers our ability to fully evaluate and optimize treatment strategies. To model this clinically relevant phenomenon, we generated single (sKO), double (dKO), and triple (tKO) knockout Raji lymphoma cell lines targeting CD19, CD20, and CD22 using CRISPR/Cas9 genome editing. Initially, we established a dual-reporter cell line expressing the fluorescent marker mCherry and the bioluminescent marker Luciferase, enabling a uniform luminescence background across all the knockout cell lines before performing the CRISPR/Cas9 editing. The loss of individual or combinatorial TAAs was validated at the genomic, transcript, and protein levels. Functional co-culture assays with antigen-specific CAR-T cells showed that antigen-deficient Raji cells resisted CAR-T cell-mediated killing, closely mimicking clinical relapse. The triple knockout (tKO) model, in particular, provided a superior system compared to commonly used K562 models, as it retains the same lymphoma background while eliminating the crucial antigenic targets, thus better simulating resistance to CAR-T cell therapy. These antigen-loss models serve as valuable tools for studying mechanisms of CAR-T cell resistance and evaluating next-generation, multi-targeting CAR-T cell therapies.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1649993"},"PeriodicalIF":5.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consumer choices regarding genome-edited food crops: lessons from Japan.","authors":"Tetsuya Ishii","doi":"10.3389/fgeed.2025.1672358","DOIUrl":"10.3389/fgeed.2025.1672358","url":null,"abstract":"<p><p>Japan has rapidly deregulated certain types of agricultural genome editing, yet the societal integration of these products warrants further investigation. This paper analyzed the sale and people's perception of genome-edited food crops in Japan after reviewing the regulatory framework. Of four genome-edited crops approved as non-genetically modified organism, only one is sold online to consumers who credit safety information and perceive usefulness. Some consumers express deep safety concern, advocating mandatory labeling. The majority of people are not sufficiently aware of genome editing. To enhance informed consumer choices of genome-edited food crops, it is crucial to share visions in society, hold risk communication for mutual understanding, and maintain clear labels, including organic food standards.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1672358"},"PeriodicalIF":4.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Insights in genome editing in human health and disease 2023/2024.","authors":"Baisong Lu, Haiwei Mou, Chen Liang","doi":"10.3389/fgeed.2025.1697828","DOIUrl":"10.3389/fgeed.2025.1697828","url":null,"abstract":"","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1697828"},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}