Frontiers in genome editing最新文献

Efficient GBA1 editing via HDR with ssODNs by outcompeting pseudogene-mediated gene conversion upon CRISPR/Cas9 cleavage. 利用ssODNs通过HDR高效编辑GBA1，在CRISPR/Cas9切割上胜过假基因介导的基因转换。

IF 4.9

Frontiers in genome editing Pub Date : 2025-04-30 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1581743

Joseph S Lagas, Monica F Sentmanat, Xiaoxia Cui

{"title":"Efficient GBA1 editing via HDR with ssODNs by outcompeting pseudogene-mediated gene conversion upon CRISPR/Cas9 cleavage.","authors":"Joseph S Lagas, Monica F Sentmanat, Xiaoxia Cui","doi":"10.3389/fgeed.2025.1581743","DOIUrl":"https://doi.org/10.3389/fgeed.2025.1581743","url":null,"abstract":"Introduction: CRISPR/Cas9-edited induced pluripotent stem cells (iPSCs) are valuable research models for mechanistic studies. However, gene conversion between a gene-pseudogene pair that share high sequence identity and form direct repeats in proximity on the same chromosome can interfere with the precision of gene editing. Mutations in the human beta-glucocerebrosidase gene (GBA1) are associated with Gaucher disease, Parkinson's disease, and Lewy body dementia. During the creation of a GBA1 KO iPSC line, we detected about 70% gene conversion from its pseudogene GBAP1. These events maintained the reading frame and resulted from GBA1-specific cleavage by CRISPR/Cas9, without disrupting the GBA1 gene.Method: To increase the percentage of alleles with out-of-frame indels for triggering nonsense-mediated decay of the GBA1 mRNA, we supplied the cells with two single-stranded oligodeoxynucleotide (ssODN) donors as homology-directed repair (HDR) templates.Results: We demonstrate that HDR using the ssODN templates effectively competes with gene conversion and enabled biallelic KO clone isolation, whereas the nonallelic homologous recombination (NAHR)-based deletion rate remained the same.Discussion: Here, we report a generalizable method to direct cellular DNA repair of double strand breaks at a target gene towards the HDR pathway using exogenous ssODN templates, allowing specific editing of one gene in a gene-pseudogene pair without disturbing the other.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1581743"},"PeriodicalIF":4.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082408","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}

引用次数: 0

Unraveling the future of genomics: CRISPR, single-cell omics, and the applications in cancer and immunology. 揭示基因组学的未来：CRISPR，单细胞组学，以及在癌症和免疫学中的应用。

IF 4.9

Frontiers in genome editing Pub Date : 2025-04-11 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1565387

A Vipin Menon, Bicna Song, Lumen Chao, Diksha Sriram, Pamela Chansky, Ishnoor Bakshi, Jane Ulianova, Wei Li

{"title":"Unraveling the future of genomics: CRISPR, single-cell omics, and the applications in cancer and immunology.","authors":"A Vipin Menon, Bicna Song, Lumen Chao, Diksha Sriram, Pamela Chansky, Ishnoor Bakshi, Jane Ulianova, Wei Li","doi":"10.3389/fgeed.2025.1565387","DOIUrl":"https://doi.org/10.3389/fgeed.2025.1565387","url":null,"abstract":"The CRISPR system has transformed many research areas, including cancer and immunology, by providing a simple yet effective genome editing system. Its simplicity has facilitated large-scale experiments to assess gene functionality across diverse biological contexts, generating extensive datasets that boosted the development of computational methods and machine learning/artificial intelligence applications. Integrating CRISPR with single-cell technologies has further advanced our understanding of genome function and its role in many biological processes, providing unprecedented insights into human biology and disease mechanisms. This powerful combination has accelerated AI-driven analyses, enhancing disease diagnostics, risk prediction, and therapeutic innovations. This review provides a comprehensive overview of CRISPR-based genome editing systems, highlighting their advancements, current progress, challenges, and future opportunities, especially in cancer and immunology.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1565387"},"PeriodicalIF":4.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001420","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}

引用次数: 0

Mapping the therapeutic landscape of CRISPR-Cas9 for combating age-related diseases. 绘制CRISPR-Cas9对抗年龄相关疾病的治疗前景

IF 4.9

Frontiers in genome editing Pub Date : 2025-04-04 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1558432

Qiyu He, Yida Wang, Zhimin Tan, Xian Zhang, Chao Yu, Xiaoqin Jiang

{"title":"Mapping the therapeutic landscape of CRISPR-Cas9 for combating age-related diseases.","authors":"Qiyu He, Yida Wang, Zhimin Tan, Xian Zhang, Chao Yu, Xiaoqin Jiang","doi":"10.3389/fgeed.2025.1558432","DOIUrl":"https://doi.org/10.3389/fgeed.2025.1558432","url":null,"abstract":"CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) has emerged as a transformative genome-editing tool with significant therapeutic potential for age-related diseases, including Alzheimer's disease, Parkinson's disease, cardiovascular disorders, and osteoporosis. This study presents a bibliometric analysis of CRISPR-Cas9 research in age-related diseases, identifying key contributors, major research hotspots, and critical technological advancements. While promising applications have been demonstrated in gene repair, functional regulation, and molecular interventions, significant barriers persist, including off-target effects, low delivery efficiency, and limited editing in non-dividing cells. Ethical concerns over germline editing and gaps in long-term safety data further complicate clinical translation. Future directions emphasize the development of high-precision Cas9 variants, homology-directed repair-independent tools, and efficient delivery systems, alongside the establishment of international regulatory frameworks and multicenter clinical trials. These efforts are essential to fully realize the potential of CRISPR-Cas9 in addressing the global health challenges of aging.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1558432"},"PeriodicalIF":4.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060339","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}

引用次数: 0

CRISPR-dependent base editing as a therapeutic strategy for rare monogenic disorders. 依赖crispr的碱基编辑作为罕见单基因疾病的治疗策略。

IF 4.9

Frontiers in genome editing Pub Date : 2025-04-02 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1553590

Júlia-Jié Cabré-Romans, Raquel Cuella-Martin

{"title":"CRISPR-dependent base editing as a therapeutic strategy for rare monogenic disorders.","authors":"Júlia-Jié Cabré-Romans, Raquel Cuella-Martin","doi":"10.3389/fgeed.2025.1553590","DOIUrl":"https://doi.org/10.3389/fgeed.2025.1553590","url":null,"abstract":"Rare monogenic disorders are caused by mutations in single genes and have an incidence rate of less than 0.5%. Due to their low prevalence, these diseases often attract limited research and commercial interest, leading to significant unmet medical needs. In a therapeutic landscape where treatments are targeted to manage symptoms, gene editing therapy emerges as a promising approach to craft curative and lasting treatments for these patients, often referred to as \"one-and-done\" therapeutics. CRISPR-dependent base editing enables the precise correction of genetic mutations by direct modification of DNA bases without creating potentially deleterious DNA double-strand breaks. Base editors combine a nickase version of Cas9 with cytosine or adenine deaminases to convert C·G to T·A and A·T to G·C, respectively. Together, cytosine (CBE) and adenine (ABE) base editors can theoretically correct ∼95% of pathogenic transition mutations cataloged in ClinVar. This mini-review explores the application of base editing as a therapeutic approach for rare monogenic disorders. It provides an overview of the state of gene therapies and a comprehensive compilation of preclinical studies using base editing to treat rare monogenic disorders. Key considerations for designing base editing-driven therapeutics are summarized in a user-friendly guide for researchers interested in applying this technology to a specific rare monogenic disorder. Finally, we discuss the prospects and challenges for bench-to-bedside translation of base editing therapies for rare monogenic disorders.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1553590"},"PeriodicalIF":4.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032174","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}

引用次数: 0

Cas9 endonuclease: a molecular tool for in vitro cloning and CRISPR edit detection. Cas9内切酶：体外克隆和CRISPR编辑检测的分子工具。

IF 4.9

Frontiers in genome editing Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1565297

Xingliang Ma, Dhouha Kthiri, Manpartik S Gill, Curtis J Pozniak, Sateesh Kagale

引用次数: 0

CRISPR/Cas9: a sustainable technology to enhance climate resilience in major Staple Crops. CRISPR/Cas9：增强主要主粮作物气候适应能力的可持续技术

IF 4.9

Frontiers in genome editing Pub Date : 2025-03-18 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1533197

Navjot Kaur, Muslim Qadir, Dali V Francis, Anshu Alok, Siddharth Tiwari, Zienab F R Ahmed

{"title":"CRISPR/Cas9: a sustainable technology to enhance climate resilience in major Staple Crops.","authors":"Navjot Kaur, Muslim Qadir, Dali V Francis, Anshu Alok, Siddharth Tiwari, Zienab F R Ahmed","doi":"10.3389/fgeed.2025.1533197","DOIUrl":"10.3389/fgeed.2025.1533197","url":null,"abstract":"Climate change is a global concern for agriculture, food security, and human health. It affects several crops and causes drastic losses in yield, leading to severe disturbances in the global economy, environment, and community. The consequences on important staple crops, such as rice, maize, and wheat, will worsen and create food insecurity across the globe. Although various methods of trait improvements in crops are available and are being used, clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) mediated genome manipulation have opened a new avenue for functional genomics and crop improvement. This review will discuss the progression in crop improvement from conventional breeding methods to advanced genome editing techniques and how the CRISPR/Cas9 technology can be applied to enhance the tolerance of the main cereal crops (wheat, rice, and maize) against any harsh climates. CRISPR/Cas endonucleases and their derived genetic engineering tools possess high accuracy, versatile, more specific, and easy to design, leading to climate-smart or resilient crops to combat food insecurity and survive harsh environments. The CRISPR/Cas9-mediated genome editing approach has been applied to various crops to make them climate resilient. This review, supported by a bibliometric analysis of recent literature, highlights the potential target genes/traits and addresses the significance of gene editing technologies in tackling the vulnerable effects of climate change on major staple crops staple such as wheat, rice, and maize.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1533197"},"PeriodicalIF":4.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765670","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}

引用次数: 0

Emerging applications of gene editing technologies for the development of climate-resilient crops. 基因编辑技术在气候适应型作物开发中的新兴应用。

IF 4.9

Frontiers in genome editing Pub Date : 2025-03-10 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1524767

R L Chavhan, S G Jaybhaye, V R Hinge, A S Deshmukh, U S Shaikh, P K Jadhav, U S Kadam, J C Hong

{"title":"Emerging applications of gene editing technologies for the development of climate-resilient crops.","authors":"R L Chavhan, S G Jaybhaye, V R Hinge, A S Deshmukh, U S Shaikh, P K Jadhav, U S Kadam, J C Hong","doi":"10.3389/fgeed.2025.1524767","DOIUrl":"10.3389/fgeed.2025.1524767","url":null,"abstract":"Climate change threatens global crop yield and food security due to rising temperatures, erratic rainfall, and increased abiotic stresses like drought, heat, and salinity. Gene editing technologies, including CRISPR/Cas9, base editors, and prime editors, offer precise tools for enhancing crop resilience. This review explores the mechanisms of these technologies and their applications in developing climate-resilient crops to address future challenges. While CRISPR/enables targeted modifications of plant DNA, the base editors allow for direct base conversion without inducing double-stranded breaks, and the prime editors enable precise insertions, deletions, and substitutions. By understanding and manipulating key regulator genes involved in stress responses, such as DREB, HSP, SOS, ERECTA, HsfA1, and NHX; crop tolerance can be enhanced against drought, heat, and salt stress. Gene editing can improve traits related to root development, water use efficiency, stress response pathways, heat shock response, photosynthesis, membrane stability, ion homeostasis, osmotic adjustment, and oxidative stress response. Advancements in gene editing technologies, integration with genomics, phenomics, artificial intelligence (AI)/machine learning (ML) hold great promise. However, challenges such as off-target effects, delivery methods, and regulatory barriers must be addressed. This review highlights the potential of gene editing to develop climate-resilient crops, contributing to food security and sustainable agriculture.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1524767"},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702393","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}

引用次数: 0

CRISPR-mediated genome editing of wheat for enhancing disease resistance. CRISPR-mediated genome editing of wheat for enhancing disease resistance.

IF 4.9

Frontiers in genome editing Pub Date : 2025-02-25 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1542487

Joshua Waites, V Mohan Murali Achary, Easter D Syombua, Sarah J Hearne, Anindya Bandyopadhyay

{"title":"CRISPR-mediated genome editing of wheat for enhancing disease resistance.","authors":"Joshua Waites, V Mohan Murali Achary, Easter D Syombua, Sarah J Hearne, Anindya Bandyopadhyay","doi":"10.3389/fgeed.2025.1542487","DOIUrl":"10.3389/fgeed.2025.1542487","url":null,"abstract":"Wheat is cultivated across diverse global environments, and its productivity is significantly impacted by various biotic stresses, most importantly but not limited to rust diseases, Fusarium head blight, wheat blast, and powdery mildew. The genetic diversity of modern cultivars has been eroded by domestication and selection, increasing their vulnerability to biotic stress due to uniformity. The rapid spread of new highly virulent and aggressive pathogen strains has exacerbated this situation. Three strategies can be used for enhancing disease resistance through genome editing: introducing resistance (R) gene-mediated resistance, engineering nucleotide-binding leucine-rich repeat receptors (NLRs), and manipulating susceptibility (S) genes to stop pathogens from exploiting these factors to support infection. Utilizing R gene-mediated resistance is the most common strategy for traditional breeding approaches, but the continuous evolution of pathogen effectors can eventually overcome this resistance. Moreover, modifying S genes can confer pleiotropic effects that hinder their use in agriculture. Enhancing disease resistance is paramount for sustainable wheat production and food security, and new tools and strategies are of great importance to the research community. The application of CRISPR-based genome editing provides promise to improve disease resistance, allowing access to a broader range of solutions beyond random mutagenesis or intraspecific variation, unlocking new ways to improve crops, and speeding up resistance breeding. Here, we first summarize the major disease resistance strategies in the context of important wheat diseases and their limitations. Next, we turn our attention to the powerful applications of genome editing technology in creating new wheat varieties against important wheat diseases.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1542487"},"PeriodicalIF":4.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607414","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}

引用次数: 0

Engineering tomato disease resistance by manipulating susceptibility genes. 通过操纵易感基因来改造番茄抗病能力。

IF 4.9

Frontiers in genome editing Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1537148

Duoduo Wang, Palash Mandal, Md Sazan Rahman, Lirong Yang

{"title":"Engineering tomato disease resistance by manipulating susceptibility genes.","authors":"Duoduo Wang, Palash Mandal, Md Sazan Rahman, Lirong Yang","doi":"10.3389/fgeed.2025.1537148","DOIUrl":"10.3389/fgeed.2025.1537148","url":null,"abstract":"Various pathogens severely threaten tomato yield and quality. Advances in understanding plant-pathogen interactions have revealed the intricate roles of resistance (R) and susceptibility (S) genes in determining plant immunity. While R genes provide targeted pathogen resistance, they are often vulnerable to pathogen evolution. Conversely, S genes offer a promising avenue for developing broad-spectrum and durable resistance through targeted gene editing. Recent breakthroughs in CRISPR/Cas-based technologies have revolutionized the manipulation of plant genomes, enabling precise modification of S genes to enhance disease resistance in tomato without compromising growth or quality. However, the utilization of the full potential of this technique is challenging due to the complex plant-pathogen interactions and current technological limitations. This review highlights key advances in using gene editing tools to dissect and engineer tomato S genes for improved immunity. We discuss how S genes influence pathogen entry, immune suppression, and nutrient acquisition, and how their targeted editing has conferred resistance to bacterial, fungal, and viral pathogens. Furthermore, we address the challenges associated with growth-defense trade-offs and propose strategies, such as hormonal pathway modulation and precise regulatory edits, to overcome these limitations. This review underscores the potential of CRISPR-based approaches to transform tomato breeding, paving the way for sustainable production of disease-resistant cultivars amidst escalating global food security challenges.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1537148"},"PeriodicalIF":4.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494625","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}

引用次数: 0

Editorial: Insights in genome editing in animals 2023/2024. 社论：2023/2024年动物基因组编辑的见解。

IF 4.9

Frontiers in genome editing Pub Date : 2025-01-23 eCollection Date: 2025-01-01 DOI: 10.3389/fgeed.2025.1556425

Gӧtz Laible, Mark Cigan

引用次数: 0