gene editing

基于生物网络的动态拓扑优化

This paper explores the application of dynamic topology optimization techniques to biological networks, aiming to enhance drug discovery and gene editing. Biological networks, complex systems of interconnected nodes and edges, are increasingly utilized in various fields. Traditional optimization methods often rely on fixed parameters, failing to fully exploit the inherent structure and dynamic properties of these networks. We propose a novel framework that leverages the topology of biological networks, employing dynamic optimization algorithms to iteratively refine network parameters and achieve optimal configurations. This research focuses on a specific example – protein-protein interaction networks – demonstrating the potential of this approach to improve network stability and functional efficiency. The core mechanism involves analyzing network topology, identifying critical nodes, and dynamically adjusting parameters to promote convergence and improve overall network performance. This work contributes to the development of more robust and effective strategies for optimizing biological networks.

A national framework for managing dual-use research of concern: integrating biosecurity, public health, and research governance

Dual-use research of concern (DURC)—legitimate life-science research that could be misapplied to cause significant harm—has become an increasingly urgent policy challenge. Advances in synthetic biology, gene editing, and artificial intelligence have expanded both the pace and diffusion of high-risk biological work, while governance systems remain fragmented across national boundaries. Based on a structured narrative policy review updated through 28 July 2026, this article proposes a comprehensive national DURC risk-management program that bridges biosecurity, public health, research governance, and emergency management. Drawing on the World Health Organization’s 2022 Global Guidance Framework for the Responsible Use of the Life Sciences, the ISO 35001:2019 biorisk management standard, and national policy precedents—including the design of the 2024 U.S. Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential (DURC-PEPP Policy), whose planned implementation was superseded by Executive Order 14,292 while a revised or replacement federal policy remained under development at the final search date—the article maps five overlapping threat pathways relevant to DURC governance, analyzes their multi-layered consequences, and identifies existing tools and stakeholder interfaces that can be adapted. The core of the framework comprises eleven integrated recommendations across prevention and response domains: establishing a national DURC governance structure, strengthening institutional oversight and ethics review, implementing laboratory biorisk management systems, addressing cyberbiosecurity, mitigating insider threats, promoting responsible communication safeguards, enhancing early detection and surveillance, developing DURC-specific emergency response plans, protecting first responders and healthcare workers, institutionalizing risk communication and public engagement, and embedding continuous learning and international collaboration. The program emphasizes the protection of frontline workers, the integration of occupational health into biosecurity planning, and the institutionalization of intersectoral coordination mechanisms. Achieving these goals requires sustained collaboration across health, security, research, digital, and community sectors, but the benefits extend beyond DURC, enhancing national preparedness for all biological threats.

Molecular Scissors With a Search Bar: A Historical Development Review of CRISPR and the Editing of the Genome

This article presents a narrative review of CRISPR and the Editing of the Genome in the context of Biology. The literature on this topic has expanded substantially over recent decades, yet it remains fragmented across subfields, methods, and national research traditions. Drawing on an interpretive synthesis of representative contributions, the review reconstructs the historical development of the area, examines the conceptual foundations and definitional disputes that organize its debates, and maps the contemporary landscape of research, including the methodological shift toward data-intensive approaches and the institutional pressures that shape publication practice. Particular attention is given to the role of CRISPR and gene editing as organizing themes, and to the conditions under which findings from different research traditions can be brought into productive comparison. The review identifies three synthetic conclusions: the literature is cumulatively strong but organizationally weak; methodological pluralism is better understood as a resource than as a defect; and the growing practical salience of the topic raises the stakes of its unresolved conceptual questions. An agenda for future work is proposed, emphasizing integrative research designs, transparent synthesis practices, and the protection of definitional and infrastructural work on which cumulative progress depends. The article is intended as both a reference map for newcomers and a provocation for specialists in Biology.

Lipopolymer Nanoparticle-Mediated In Vivo CRISPR-Cas9 Editing of Mrg15 Restores Mitochondrial Mitophagy to Alleviate Metabolic-Associated Steatohepatitis.

Metabolic-associated steatohepatitis (MASH) remains difficult to treat due to the lack of interventions capable of targeting upstream disease drivers and achieving durable disease modification. The epigenetic regulator Mrg15 has been implicated in mitochondrial dysfunction and metabolic stress in the liver, suggesting its potential relevance to MASH pathogenesis. Here, we develop a liver-targeted lipopolymer nanoparticle (LPNP)-mediated gene editing platform to enable in vivo disruption of Mrg15 by co-delivery of Cas9 mRNA and Mrg15 sgRNA. The screened P64H/Mrg15 system achieved efficient hepatic delivery and genome editing, resulting in reduced Mrg15 expression in hepatocytes. In the MASH mouse model, P64H/Mrg15 treatment was associated with decreased hepatic lipid accumulation, improved liver injury markers, and attenuation of inflammation and fibrosis. Sequence-level analyses confirmed on-target editing in liver tissue, and systemic histopathological evaluation revealed no overt toxicity in major organs under the tested dosing regimen. Transcriptomic profiling revealed coordinated pathway-level associations involving metabolic, inflammatory, and autophagy-related regulation, while protein-level analyses demonstrated alterations in selected autophagy- and mitophagy-related regulators, including TUFM and LC3B-II. Together, these findings identify Mrg15 as a disease-relevant epigenetic regulator in MASH and highlight liver-directed P64H LPNP/CRISPR delivery as a promising non-viral strategy for modulating upstream regulatory pathways in metabolic liver disease.

Insights into fodder quality enhancement in sorghum through genetic and molecular approaches

Forage sorghum (Sorghum bicolor L. Moench), a climate-resilient, drought-tolerant fodder crop with high adaptability and biomass potential, plays a significant role in addressing global livestock feed and fodder demands. However, its complex quantitative quality traits, such as crude protein, fibre fractions, crude fat, lignin and antinutritional factors like hydrogen cyanide (HCN) content, show considerable variation across genotypes and are strongly influenced by developmental stage, management practices and environmental conditions. This review comprehensively summarises the genetic and molecular strategies for improving forage quality traits in sorghum, highlighting key trait relationships, yield-quality trade-offs, harvesting effects and emerging genomic tools to accelerate the development of nutritionally superior and safer forage sorghum cultivars. Conventional breeding programs have contributed to the development of improved forage sorghum cultivars. Brown midrib lines have emerged as a successful breeding strategy, with average neutral detergent fibre (NDF) and acid detergent fibre (ADF) contents of 57.5 % and 33.67 % dry matter (DM), compared to 59.45 % and 36.51 % DM in conventional varieties. However, this is often accompanied by biomass yield penalties of approximately 14.33 %. Recent advances in molecular breeding, such as functional genomics, genome-wide association studies (GWAS), quantitative trait loci (QTL) mapping, marker-assisted selection and antisense-mediated downregulation, have enabled the precise identification of the genetic architecture of forage quality traits. In particular, QTL mapping uncovered 43 overlapping QTLs controlling various forage quality traits and biomass traits, demonstrating their interconnections and possibilities for their simultaneous improvement. The identified candidate genes and pleiotropic loci controlling forage quality traits offer new opportunities for genomic-assisted improvement, where gene-editing tools such as CRISPR/Cas9 can simultaneously enhance feed safety, biomass yields and nutritional quality.

Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN): integrating epidemiological insights with diagnostic and therapeutic progress

Abstract Background Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive, fatal multisystem disorder characterized by significant genotypic and geographic heterogeneity. Despite recent therapeutic breakthroughs, overlapping clinical features frequently lead to misdiagnosis and delayed intervention. Methods A comprehensive narrative review of the literature was conducted to synthesize recent advancements in the epidemiology, diagnostic workflows, and therapeutic landscape of ATTRv-PN, with an emphasis on clinical translation and multidisciplinary management. Results The epidemiological profile of ATTRv-PN highlights region-specific variant distributions (e.g., p.Val50Met, p.Ala117Ser). The diagnostic paradigm has shifted towards prioritizing early genetic testing and minimally invasive biopsies, complemented by emerging serum biomarkers like neurofilament light chain (NfL) and advanced neuroimaging. Therapeutically, the landscape has been transformed by disease-modifying therapies (DMTs). Gene-silencing agents (siRNAs and ASOs) and TTR stabilizers have demonstrated robust efficacy in halting neuropathy progression. Furthermore, novel modalities, including amyloid-depleting monoclonal antibodies and in vivo CRISPR/Cas9 gene-editing therapies, show unprecedented promise in ongoing clinical trials. Conclusions ATTRv-PN has entered an era of precision medicine. Overcoming diagnostic delays through “red-flag” recognition and routine genetic screening is imperative. Early, stage-adapted initiation of DMTs within a multidisciplinary care framework is crucial for optimizing long-term patient outcomes.

Targeting TaNSUN2 provides a potential route to combine antiviral resistance with improved productivity in wheat

Research on crop disease has shifted from a single pathogen-host framework toward a multifactorial host-microbiota-environment framework. This transition, captured by the pathobiome concept, redirects attention from individual pathogens to the broader biological networks that condition disease establishment, progression, and outcome [1].In plants, disease can therefore be considered within a microbiota-aware framework in which pathogen success is shaped by host genotype, environment, and surrounding microbial consortia, including their ecological reassembly during infection.Within this broader context, host susceptibility factors are important because they can influence pathogen fitness as well as the infection-prone physiological state of the host.TaNSUN2 as a host factor co-opted by Chinese wheat mosaic virus (CWMV), and show that weakening this dependency enhances antiviral resistance while improving yieldrelated traits [2]. The study motivates two linked questions: how does CWMV redirect TaNSUN2 to control viral RNA fate, and can homoeolog-specific perturbation reduce this dependency without imposing a productivity penalty? The working hypothesis developed here is that a discrete TaeEF1A-TaNSUN2 recruitment module, rather than the entirety of TaNSUN2 function, constitutes a tractable susceptibility node. From a pathobiome-aware perspective, this is a virus-exploited epitranscriptomic hostdependency module; however, the study does not directly demonstrate restructuring of the wider pathobiome.CWMV is a soil-borne, bipartite positive-sense RNA furovirus that infects wheat and is transmitted to roots by the obligate plasmodiophorid Polymyxa graminis [3]. Infection produces chlorotic mosaic symptoms and stunting in winter wheat, while long-lived vector resting spores make eradication from infested soil difficult. Resistant cultivars therefore remain the most practical management option, which gives particular agricultural relevance to host susceptibility factors that can be modified without compromising yield.RNA modifications are central post-transcriptional regulators of RNA metabolism and gene expression in eukaryotes [4]. Among them, m5C influences RNA stability, export, translation, and stress adaptation [5; 6]. Chemically, m5C is installed by S-adenosyl-Lmethionine-dependent RNA cytosine-5 methyltransferases through a conserved catalytic cysteine and a covalent enzyme-RNA intermediate [5; 6]. In mammals, NSUN2 is a major mRNA m5C writer, whereas ALYREF and YBX1 recognize or bind m5C-modified transcripts to regulate export and stability [7; 8]. In plants, transcriptome-wide analyses have detected m5C in coding and noncoding RNAs and linked it to development and environmental responses. In Arabidopsis, TRM4B functions as an RNA m5C writer; trm4b mutants show reduced m5C, altered stability of target transcripts, and root-development defects [9]. In rice, OsNSUN2 maintains mRNA m5C methylation and supports growth under elevated temperature [10]. Plant m5C readers and erasers remain less completely defined, and it was unclear whether a virus could redirect a host m5C writer to viral RNA and whether such exploitation could be disrupted without an agronomic penalty.Plant-virus epitranscriptomics has so far been shaped largely by studies of N6methyladenosine (m6A), which can have opposing effects in different virus-host combinations. In Arabidopsis, the m6A demethylase ALKBH9B promotes alfalfa mosaic virus infection and vascular movement [11; 12], whereas YTH-domain ECT proteins recognize m6A-marked viral RNA and contribute to antiviral restriction [13].In wheat, TaHAKAI has context-dependent functions during wheat yellow mosaic virus infection: its m6A-writer activity can favor viral RNA accumulation, while its E3-ligase activity promotes degradation of a viral silencing suppressor and is linked to favorable spike traits [14]. Recent tomato profiling further showed that tomato spotted wilt virus reshapes the host m5C landscape and that SlTRM4B stabilizes defense-related host transcripts [15]. These comparisons underscore that the outcome of an RNA modification depends on the modified substrate, the reader or effector recruited, and the viral context. The TaNSUN2 study is distinctive because it directly links m5C deposition on viral RNA with homoeolog-specific functional differentiation and favorable agronomic consequences.Jiang et al. address this unresolved m5C question directly. CWMV does not appear to recruit TaNSUN2 on its own; instead, it co-opts the host translation elongation factor TaeEF1A, which recruits TaNSUN2 to viral replication complexes (VRCs). Within VRCs, TaNSUN2 deposits m5C on viral RNAs, increasing RNA stability and translational efficiency. m5C deposition in the viral 3′ untranslated region has two complementary effects: it strengthens the association of TaeEF1A with viral RNA to support replication and enhances coat-protein binding to promote virion assembly. Thus, CWMV repurposes host m5C machinery at multiple stages of infection, providing a direct example of viral exploitation of an epitranscriptomic regulator.A particularly important aspect of the study is that resistance arises by weakening a defined host-virus molecular interface rather than by eliminating all TaNSUN2 activity. Natural allelic variation in TaNSUN2 reduces its affinity for TaeEF1A, thereby limiting recruitment to viral replication complexes and attenuating proviral activity without broadly disrupting host RNA metabolism. This distinction matters because resistance may be achieved not only by knocking out susceptibility genes, but also by selectively disrupting the pathogen-dependent interaction while preserving endogenous functions. This principle aligns with a broader trend in plant disease biology: host dependency often resides in discrete molecular interfaces rather than in the entirety of a host protein's physiological role. The susceptibility-gene framework likewise emphasizes that loss or modification of host compatibility factors can provide resistance, while pleiotropic effects must be evaluated case by case [16; 17]. TaNSUN2 is therefore especially relevant to breeding because naturally occurring or engineered variants could preserve core endogenous functions while diminishing pathogen exploitation. A related principle is illustrated by the Rice grassy stunt virus (RGSV) P3-D14/SL pathway, in which infection depends on a specific interaction with a host hormone receptor to hijack strigolactone signaling and suppress antiviral RNA interference [18]. Precise modification of this interaction interface can confer robust resistance without substantial growth or yield penalties.Particularly noteworthy is the agronomic outcome of perturbing TaNSUN2. Jiang et al.report that knockout of TaNSUN2-5A markedly enhances CWMV resistance, increases thousand-grain weight by approximately 5.9 g, improves grain length and width, and raises yield per plant by more than 14%. Under the genetic background and conditions examined, enhanced antiviral resistance therefore did not require a detectable productivity trade-off. This result supports a cautious interpretation: TaNSUN2-5A is a promising route for combining resistance with favorable yield-related traits, although it does not yet establish a general mechanistic uncoupling of susceptibility from productivity.One plausible explanation for this favorable outcome is homoeolog specialization.Because the three TaNSUN2 copies are not functionally equivalent, selective perturbation of TaNSUN2-5A may strengthen antiviral defense while the other copies retain essential endogenous functions. Polyploid redundancy therefore becomes an opportunity for allele-specific or copy-specific intervention rather than only an obstacle to genotype-phenotype analysis. Such subfunctionalization could buffer developmental costs and permit finer adjustment than would be possible in a single-copy system.Nevertheless, the causal contribution of homoeolog specialization to the favorable yield phenotype remains to be resolved.Viewed in this way, the study does more than identify a susceptibility factor. It offers a potential route toward precision breeding in which resistance is combined with preserved or improved yield. This favorable combination makes TaNSUN2 relevant beyond the immediate wheat-CWMV system. Nevertheless, broader applicability will require direct testing across additional viruses, wheat backgrounds, and environmental conditions.Within a pathobiome-aware framework, host regulators that alter both pathogen fitness and host physiology can be considered candidate nodes of disease compatibility, although such network-level effects have not been demonstrated for TaNSUN2. This framing is relevant in wheat because the three TaNSUN2 homoeologs are not equivalent: TaNSUN2-5A is preferentially associated with the viral response, whereas TaNSUN2-5B appears more closely linked to root development. TaNSUN2 may therefore be viewed as a dosage-sensitive regulatory node at the intersection of epitranscriptomic control, polyploid genome organization, and disease compatibility. Targeting one homoeolog could potentially shift viral compatibility while other copies maintain the broader developmental program. This remains a hypothesis-generating interpretation and should not be taken as evidence that TaNSUN2 remodels rhizosphere or phyllosphere communities.Parallel evidence from tropical polyploid and clonally propagated crops supports the broader breeding logic. Cultivated banana germplasm arose through hybridization and polyploidization and is characterized by high heterozygosity, clonal propagation, and reduced fertility, all of which complicate conventional resistance breeding [19].Nevertheless, susceptibility-focused genome editing has proved effective: editing the banana DMR6 orthologue enhanced resistance to bacterial disease [20], and targeted knockout of MusaENODL3 increased resistance to Xanthomonas wilt [21]. These studies do not identify TaNSUN2-like epitranscriptomic regulators, but they show that host-encoded vulnerability nodes can be reconfigured in genetically complex crops.The comparison therefore concerns a shared breeding logic, not a shared TaNSUN2 pathway.A related pattern is emerging in sugarcane, another highly polyploid crop in which conventional breeding is constrained by genome complexity and redundancy [22].Recent studies identify actionable host-side targets, including the negative regulators ScWRKY2 and ScCAX4 [23; 24], and virus-exploited host factors such as ScHSP17.5 and ScHSP17.9A, which facilitate sugarcane mosaic virus replication [25]. Together, these findings suggest that crop improvement in complex genomes may benefit from identifying and weakening recurrent host dependencies. In this context, TaNSUN2 should be viewed as a candidate host-dependency node whose possible pathobiomelevel relevance remains a testable hypothesis.

Deciphering abiotic stress resilience in crop plants through multiomics insights and CRISPR Cas9 mediated genome editing

Abiotic factors, such as drought, salt, severe temperatures, and heavy metal toxicity, persistently threaten global agricultural production, contributing to an estimated 40–70% of yield losses in primary food crops globally. Drought diminishes yields by as much as 50% in rice, 42% in soybean, 40% in maize, 21% in wheat, and 27–40% in chickpea, while soil salinity, impacting almost 20% of irrigated agricultural area, induces similar productivity declines. In a similar vein, temperature extremes and heavy metal toxicity worsen oxidative stress, hinder nutrient uptake, and upset cellular homeostasis, all of which impede plant growth and development. Genomics and proteomics profiling have enabled the systematic identification and functional characterization of stress-responsive genes (e.g., OsPYL9, AtWRKY8) and regulatory proteins, including heat shock protein 70 (HSP70) and glutathione transferase, which mediate stress perception and downstream adaptive signaling cascades. CRISPR-based genome editing provides a precise and promising approach for developing climate-resilient crops by targeting key gene (cytokinins oxidase gene (OsCKX2)) involved in abiotic stress tolerance, offering potential for sustainable crop improvement under changing environmental conditions.This study assesses the state of CRISPR/Cas9-based genome editing for stress tolerance, highlights the molecular and regulatory underpinnings of abiotic variables in agricultural plants. Additionally, it is expected that advancements in genome editing technologies (such as CRISPR-Cas9) and high-resolution proteomic methods would provide new options for precision agricultural trait alteration, enhancing breeding programs and aiding global efforts to assure food security. Plant survival is impacted by cellular alterations brought on by abiotic stress. Proteomics and genomics are dynamic fields of study that examine genes and proteins involved in stress tolerance. Identification of genes involved in combating abiotic stress and the understanding of their functions aid scientists in developing varieties that are resistant to various types of stress.

Advances in Sexual and Asexual Propagation of Toxicodendron vernicifluum: Mechanisms, Technical Bottlenecks, and Industrialized Breeding Perspectives

Toxicodendron vernicifluum is an economically unique lacquer-producing tree en-demic to East Asia; propagation bottlenecks severely restrict elite clone industrializa-tion. This review systematically synthesizes 20 years of domestic and international lit-erature on seed propagation, root cutting, stem cutting, grafting, and tissue culture of lacquer tree, compares technical performance among China, Japan, Vietnam, and Med-iterranean Rhus species, and quantitatively summarizes germination/rooting rates across protocols. Sexual propagation suffers from seed deep dormancy and progeny segregation; conventional asexual propagation has low rooting efficiency; tissue culture faces high cost and browning obstacles; molecular regulatory mechanisms remain poorly characterized. We propose an integrated breeding framework combining mo-lecular mechanism dissection, low-cost vegetative propagation optimization, and standardized seedling production. Future directions including multi-omics analysis, gene-edited easy-rooting germplasm, and bioreactor micropropagation are highlighted to support large-scale elite seedling cultivation in Qinba Mountain regions.

Okay, here's a full-fledged paper on "基于生物信息的自适应基因编辑系统", adhering to your specifications:

This paper introduces a novel system for personalized gene editing based on dynamic gene expression modulation, leveraging biological information to tailor gene expression to individual characteristics and environmental factors. Traditional gene editing methods primarily focus on modifying genes, while this system aims to optimize individual gene function through a bio-informed approach. The core mechanism involves constructing a "bio-gene map" and dynamically adjusting gene expression to achieve improved health outcomes. This represents a significant advancement in precision medicine, offering the potential for more effective and targeted therapeutic interventions.

Dual-gRNA CRISPR/Cas9 Deletion of CsDMR6 in Sweet Orange Supported by Improved In Vitro Regeneration

Huanglongbing (HLB), caused by Candidatus Liberibacter spp., remains the most destructive disease affecting citrus worldwide. To support host-directed genome-editing strategies aimed at reducing susceptibility, we optimized key regeneration steps in Citrus sinensis and validated a dual-gRNA CRISPR/Cas9 approach targeting the susceptibility gene CsDMR6. Juvenile explants of ‘Valencia’ and hybrid genotypes (CsH1–CsH3) were successfully established in vitro, and shoot elongation was markedly improved by supplementing Citrus Shoot Multiplication (CiSM) medium with 1 mg L−1 GA3. Callus induction was most efficient in Citrus Callus Induction (CiCM) medium under dark conditions, while a 48 h NAA pulse (100 µM) significantly enhanced rooting, increasing efficiencies to 37.1% in ‘Valencia’ and 52.9% in CsH1. Two guide RNAs targeting conserved regions of CsDMR6 were designed and shown to be identical across all evaluated genotypes. The dual-gRNA cassette was assembled into a CRISPR/Cas9 geminivirus-based vector and transiently delivered into sweet orange leaf tissue via Agrobacterium. GFP fluorescence verified construct expression, and PCR amplification across the target region produced a diagnostic ~447 bp fragment corresponding to the expected ~5.8 kb deletion. Sanger sequencing confirmed precise junction formation between the two cut sites. These results demonstrate efficient large-fragment deletion of CsDMR6 in sweet orange and establish an experimentally validated, genotype-compatible regeneration and editing platform. This study provides a transient validation of the dual-gRNA system and establishes the technical foundation required for future stable, non-transgenic edited lines. Together, these advances support the downstream functional evaluation of CsDMR6 loss-of-function alleles under HLB pressure.

Evaluating Computational Tools for CRISPR-Cas9 Design: A Case Study on the TP53 Gene