Frontiers in Genome Editing
Frontiers in Genome Editing(英文缩写 FRONT GENOME EDIT),ISSN 2673-3439,eISSN 2673-3439 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-10-01 至 2026-09-30，按本站收录文献的发表日期统计。
期刊介绍
Frontiers in Genome Editing 最新收录文献
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1. A novel minimally humanized mouse model of aniridia for preclinical evaluation of CRISPR gene editing strategies.
PMID:日期:2026-09-18Aniridia is a rare congenital vision-loss disorder primarily caused by variants in the paired box 6 () gene. Current treatments do not maintain vision long term, nor address the underlying disease mechanism. CRISPR-mediated genome editing holds great promise for treating genetic diseases but requires demonstration of efficacy on human DNA to support translational relevance. The aim of this work was to generate and test a minimally humanized mouse model of aniridia, carrying a FLAG-tagged and the most common recurring pathogenic aniridia-patient variant, introduced for the first time in mice. Ocular assessments (gross examination, slit lamp imaging, and fluorescent and confocal microscopy) were performed in mice homozygous for humanization and heterozygous for the variant, paralleling patients. Mice were examined immediately post-wean and at adulthood, with the former chosen as a likely time for treatment initiation. As an exploratory proof-of-principle, a lipid nanoparticle-delivered adenine base editor (ABE8e) was tested to demonstrate the utility of the model. Ocular assessments revealed the expected phenotypes for an aniridia mouse model, supporting successful generation and phenotypic validation of the humanized mouse. The ABE8e treatment resulted in a modest correction (4.8% ± 0.4% SEM) of the pathogenic variant in clinically relevant ex vivo cortical neurons. Although designed for the development of genome editing therapies, this humanized mouse is also applicable to other therapies requiring interaction with human DNA or RNA. It also enables evaluation of nonsense-suppression drugs since the readthrough proteins retain the FLAG tag. More broadly, this methodology is applicable to other pathogenic variants for aniridia, CRISPRa approaches, and other genetic diseases for which CRISPR-based therapy holds promise.
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2. CRISPR/Cas9 in soybean research: a measured leap toward genetic refinement.
PMID:日期:2026-09-17Soybean [ (Linn.) Merr] is a globally important source of plant-based protein and edible oil, widely cultivated in India as a major oilseed crop. However, conventional breeding approaches for soybean are laborious, constrained by the genomic complexity of soybean, and face persistent challenges in genetic transformation. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-based genome editing has emerged as a precise and efficient tool for rapid trait improvement in soybean. While many existing reviews of soybean have been published, this literature review addresses some fundamental challenges with respect to genome editing. This study summarizes recent advancements in soybean genome editing, offering insights into the practical informatics of soybean-specific genomic databases that are required for successful construct design. It also discusses emerging technologies such as base editing, prime editing, and the increasingly important role of artificial intelligence in accelerating target identification and construct design. It highlights applications in nutritional enhancement, abiotic and biotic stress tolerance, and improvement of key agronomic traits. Beyond the conventional topics, it addresses the current regulatory landscape that researchers must navigate for releasing genome-edited varieties and provides a comprehensive perspective on practical solutions to overcome major constraints in soybean genetic engineering.
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3. Overcoming delivery barriers of large all-in-one CRISPR/Cas9 plasmids using lysine-based lipid nanoparticles.
PMID:日期:2026-09-16Lipid nanoparticles (LNPs) are widely used as drug delivery systems (DDS) for the intracellular delivery of gene-editing tools such as the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system. Previously, a lysine-headgroup cationic lipid (K3C16) was reported to exhibit high biocompatibility and cellular internalization via plasma membrane fusion when formulated as liposomes, suggesting its potential as a low-toxicity gene delivery material. However, the translation of this lipid into a multi-component lipid nanoparticle (LNP) matrix via microfluidic engineering for large cargo encapsulation has not been explored. In this study, K3C16 was successfully engineered for the first time as the main lipid component of LNPs to deliver large plasmid DNA encoding the CRISPR/Cas9 system. First, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) were evaluated as helper phospholipids to identify an optimal lipid composition. LNPs containing DOPE exhibited significantly higher transfection efficiency than those containing DOPC and were therefore selected for subsequent experiments. Next, LNPs formulated with different cationic or ionizable lipids were prepared and evaluated in HEK293 cells for transfection efficiency, cytotoxicity, and gene-editing efficiency. LNPs containing the commercial ionizable lipid SM-102 showed higher transfection and gene-editing efficiencies than the lysine-headgroup cationic lipids represent a promising and biocompatible platform for CRISPR/Cas9 plasmid delivery; however, increased cytotoxicity was observed in highly transfected cell populations. In contrast, the lysine-headgroup cationic LMPs achieved effective delivery of large plasmid DNA and CRISPR/Cas9-mediated gene editing while maintaining superior biocompatibility. These results demonstrate that lysine-headgroup cationic lipids represent a promising and biocompatible platform for CRISPR/Cas9 plasmid delivery. Further optimization of lipid composition and molar ratios may enhance transfection and gene-editing efficiencies, advancing the development of safer nonviral gene delivery systems.
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4. R2Tg retrotransposon mediated targeted integration of exogenous genes into the 28S rDNA locus in mammalian cell lines for PKU gene therapy.
PMID:日期:2026-09-15Phenylketonuria (PKU) remains a challenging genetic disorder due to the absence of therapeutic strategies capable of achieving sustained restoration of phenylalanine hydroxylase (PAH) function. Here, we employed an R2 retrotransposon in (R2Tg)-based system to enable targeted integration of exogenous PAH mRNA into the 28S ribosomal DNA (rDNA) locus of the host genome, with the goal of rescuing PAH deficiency caused by loss-of-function mutations. Experimental results demonstrated that lipid nanoparticle (LNP) delivery of R2Tg facilitated efficient site-specific integration of EGFP and PAH transgenes in mammalian cells, significantly elevating PAH mRNA and protein expression without disrupting endogenous 28S rRNA levels. These findings support the potential of this strategy as a precise genomic modification tool with promise for lifelong correction of PAH deficiency.
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5. {"_":"Advancements in CRISPR-based gene therapy for hemophilia.","i":["in vivo"]}
5. {"_":"基于CRISPR的血友病基因治疗的进展。","i":["体内"]}PMID:日期:2026-09-10Hemophilia is an X-linked hereditary bleeding disorder caused by loss-of-function mutations in the genes encoding coagulation factors, leading to excessive bleeding and potentially being life-threatening. Currently, regular treatment for hemophilia is the infusion of recombinant blood coagulation factors. This approach is not only costly but can also give rise to complications such as the development of neutralizing antibodies (Nabs), which impede the therapeutic outcome. Hemophilia is a monogenic disease, making gene therapy a promising curative measure that includes gene addition and gene editing approaches. Adeno-associated virus (AAV) vectors have gained massive attention as the premier delivery vehicle for clinical gene therapy due to their diverse tissue tropisms dictated by the natural and engineered AAV capsids, their excellent safety profile since AAVs do not cause any known human diseases, low immunogenicity, and long-lasting gene expression. Several AAV-based gene addition therapies have been approved for hemophilia B and hemophilia A, and dozens of similar AAV-based clinical trials are underway. Gene editing technologies, like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), have shown immense potential in the treatment of genetic diseases. CRISPR/Cas9-mediated transgene integration provides critical advantages over regular gene insertion therapy by enabling site-specific, targeted genomic integration rather than random integration. Clinical trials focusing on AAV-CRISPR/Cas9-mediated knock-in of human genes represent the frontier of genetic medicine, and one such prominent ongoing clinical trial for hemophilia B is designed to insert the human Factor IX gene into hepatocytes. This review outlines recent advances and feasible strategies of CRISPR/Cas9-based genome editing for hemophilia therapy, highlights the potential applications of next-generation gene editing and vector delivery technologies, and offers new insights for the advantages, limitations, and future directions for these novel treatment modalities.
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6. Clinical translation of CRISPR-Cas9 therapeutics in cancer and inherited genetic disorders.
PMID:日期:2026-09-10CRISPR-Cas9, adapted from the bacterial Type II CRISPR adaptive immune system, functions as a programmable RNA-guided endonuclease that employs a single-guide RNA to direct Cas9 to specific genomic loci. CRISPR-Cas9 has transformed targeted genome editing by replacing complex protein engineering with programmable Watson-Crick base pairing between the guide RNA and target DNA. This review was developed following a structured literature search of major biomedical databases and clinical trial registries to synthesize current evidence on the therapeutic applications of CRISPR-Cas9 in oncology and inherited genetic disorders. Clinical studies of -enhancer editing have shown fetal hemoglobin reactivation, with most evaluable participants with sickle cell disease remaining free of severe vaso-occlusive crises for the prespecified period and most evaluable participants with transfusion-dependent β-thalassemia achieving sustained transfusion independence. reductions in circulating transthyretin protein levels have been achieved for transthyretin amyloidosis via lipid nanoparticle delivery, while clinically meaningful improvements in selected measures of visual function were observed in a subset of patients receiving subretinal AAV-delivered CRISPR editing for -associated Leber congenital amaurosis type 10. Preclinical and early clinical studies have further investigated CRISPR-engineered T cells designed to improve antitumor activity, persistence, or resistance to inhibitory signaling. Despite these advances, key translational hurdles include the risk of off-target mutations and large-scale chromosomal rearrangements. Furthermore, immune responses against bacterial Cas9 nucleases and viral delivery vectors may limit the long-term efficacy of CRISPR-based therapies, while technical barriers surrounding delivery to extrahepatic tissues, such as skeletal muscle and the central nervous system, continue to hinder broader clinical success. Ethical concerns regarding germline modifications and the high cost of individualized therapies present additional translational challenges. Consequently, emerging DSB-independent technologies, such as base editing and prime editing, may reduce selected DSB-associated liabilities, but each introduces distinct editing, delivery, and genotoxicity risks that require product-specific evaluation.
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7. Rewriting the genome: harnessing R2 retrotransposons for precise DNA insertion.
PMID:日期:2026-09-04CRISPR-based genome editors are fundamentally limited by their requirement for double-strand DNA breaks (DSBs), restricted transgene cargo capacity, and reliance on error-prone endogenous DNA repair mechanisms. Non-long terminal repeat (non-LTR) retrotransposons-especially the site-specific R2 element-offer a mechanistically distinct and potentially safer choice for programmable genomic integration. These elements employ target-primed reverse transcription (TPRT)-an RNA-templated integration mechanism that circumvents DSB formation and supports amplification of self-copy. This review delineates the molecular mechanism of R2 retrotransposons, emphasizing their highly specific integration into the 28 S ribosomal DNA locus-a recognized genomic safe harbor. We describe the functional domains of the R2 protein, including the reverse transcriptase, restriction-like endonuclease, and nucleic acid-binding motifs, and explain how they coordinate to achieve precise DNA cleavage and cDNA synthesis. Recent cryo-electron microscopy (cryo-EM) structures have revealed discrete RNA-protein complex that orchestrate the stepwise progression of TPRT. Informed by these mechanistic insights, researchers have engineered programmable platforms-including PRINT and STITCHR-that enable RNA-directed transgene integration in mammalian systems. These platforms establish R2 as a viable all-RNA programmable system for targeted genomic integration. Future directions include reprogramming the DNA-binding specificity of R2 through protein engineering to target loci, optimizing integration fidelity and efficiency, and mining diverse R2-like elements from metagenomic data. With continued optimization and rigorous safety validation, R2-derived platforms could supplant current nuclease-dependent editors in applications requiring high-fidelity, large-cargo integration.
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8. Heat stress impact on rice reproductive processes: challenges and new approaches.
PMID:日期:2026-08-24Heat stress represents one of the most severe abiotic constraints to rice ( L.) productivity and is expected to intensify under ongoing climate change, particularly affecting the reproductive phase and leading to substantial yield and grain quality losses. This review synthesizes current knowledge on the impacts of heat stress on rice reproduction, with a focus on both male and female reproductive structures and their interactions. Evidence from anatomical, physiological, transcriptomic, and metabolomic studies to describe how elevated temperatures disrupt key reproductive processes, including microsporogenesis, anther dehiscence, pollen viability, pollen-pistil interactions, fertilisation, and embryo sac development were integrated in this review. It further discusses the genotype-dependent differences in reproductive thermotolerance; and key genes, metabolites, and pathways associated with heat stress perception, signalling, and tolerance are highlighted. Finally, it is briefly discussed how recent advances in breeding strategies, functional genomics and genome-editing technologies, particularly CRISPR-based approaches, are providing new opportunities to enhance reproductive resilience to heat stress and how it is essential to close the existing molecular knowledge gaps in the development of heat-tolerant rice varieties capable of sustaining productivity in a warming climate.
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9. Evaluating high-fidelity CRISPR-Cas nucleases in nucleosomal contexts using a quantitative framework.
PMID:日期:2026-08-14Chromatin presents a significant obstacle to CRISPR-Cas gene editing, as chromatin restricts nuclease access to DNA. Recent advances have produced a wide range of high-fidelity Cas9 and Cas12a variants with enhanced properties. However, their precision in targeting DNA within different contexts remains poorly understood. This gap limits our ability to predict and optimize Cas performance in the dynamic chromatin landscape. To elucidate how chromatin variability impacts Cas editing accuracy, we utilized GEMiNI-seq to systematically profile wild-type and engineered Cas9 and Cas12a nucleases across a range of nucleosome sequences. All nucleases showed reduced cleavage in nucleosomal DNA relative to naked DNA, with the strongest inhibition at dyad-proximal sites. Cleavage within nucleosomes was highly variable, with wtSpCas9 exhibiting up to 65-fold different activity depending on the nucleosome type. Editors with high catalytic activity (wtSpCas9, HIFIv2, LbCas12a ULTRA) consistently outperformed high-fidelity variants such as evoSpCas9, which displayed excellent specificity on naked DNA but poor performance in nucleosomal contexts. ROC and PRC analyses revealed that nucleosome sequence and orientation shape both sensitivity and specificity, with HIFIv1 emerging as the top-performing nuclease for nucleosomal targets, while evoSpCas9 excelled in exposed contexts. Our findings demonstrate that local nucleosome sequence and structure profoundly influence Cas nuclease accessibility and specificity. Variability in cleavage across nucleosome types underscores the need to consider chromatin context during target selection and nuclease design. These results provide a framework for selecting or engineering Cas editors optimized for therapeutic genome editing within chromatin.
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10. Beyond genes: CRISPR/Cas9 for chromosomal engineering in polyploids.
PMID:日期:2026-08-14该文献暂无摘要。