Search Results (2,028)

Hemophilias and hemoglobinopathies—including hemophilias A and B, sickle cell disease (SCD), and β-thalassemia—are debilitating genetic disorders associated with significant global health burdens. While traditional management has centered on factor replacement and transfusions, these approaches remain palliative, with limited access and durability in many regions. Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. These therapies offer durable efficacy and improved quality of life, particularly in adult populations. However, implementation remains uneven across global health systems due to high costs, limited infrastructure, and regulatory heterogeneity. Additionally, ethical considerations such as long-term surveillance, informed consent in vulnerable populations, and social perceptions of genetic modification present ongoing challenges. Innovations such as multiplex genome editing, immune-evasive donor platforms, synthetic biology, and AI-driven treatment modeling are poised to expand therapeutic horizons. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide. Full article

Background: The Dirigent (DIR) gene family is pivotal for lignin polymerization and stress adaptation in plants, yet its systematic characterization in Sorghum bicolor (S. bicolor), a critical bioenergy crop, remains underexplored. Methods: Leveraging the S. bicolor genome database, we conducted a genome-wide identification, phylogenetic classification, and expression profiling of the DIR gene family. Evolutionary dynamics, gene structure variations, promoter cis-regulatory elements, and spatiotemporal transcriptome patterns were analyzed using bioinformatics and experimental validation (RT-qPCR). Results: A total of 53 SbDIR genes were systematically identified, exhibiting uneven chromosomal distribution. Phylogenetic analysis clustered them into five clades (DIR-a, DIR-b/d, DIR-c, DIR-e, DIR-f), with subfamily-specific exon number variations suggesting functional divergence. Evolutionary studies revealed tandem duplication (TD) as the primary driver of family expansion, accompanied by strong purifying selection. Promoter analysis highlighted abundant hormone- and stress-responsive cis-elements. Tissue-specific RNA-seq data revealed root-enriched expression of SbDIR2/4/18/39/44/53, implicating their roles in root development. Notably, SbDIR39 and SbDIR53 were significantly upregulated (2.8- and 5-fold, respectively) under 150 mM NaCl stress, underscoring their stress-responsive functions. Conclusions: This study provides the first comprehensive atlas of the DIR gene family in S. bicolor, elucidating its evolutionary mechanisms and tissue-specific/stress-induced expression profiles. Key candidates (SbDIR39/53) were identified as promising targets for molecular breeding or CRISPR-based editing to enhance stress resilience in S. bicolor. These findings lay a foundation for translating genomic insights into agronomic improvements. Full article

Soybean (Glycine max L.) is an essential crop for global food, feed, and industrial applications, but its production is increasingly challenged by climate change and environmental stresses. Traditional breeding and transgenic approaches have contributed to improvements in yield and quality; however, limitations in genetic diversity and regulatory hurdles for genetically modified organisms (GMOs) underscore the need for innovative strategies to address these challenges. Genome editing technologies, particularly CRISPR/Cas9, have revolutionized soybean molecular breeding by enabling precise modifications of genes related to key agronomic traits such as yield, seed composition, and stress tolerance. These advances have accelerated the development of soybean varieties with enhanced nutritional value and adaptability. Recent progress includes improvements in editing efficiency, specificity, and the ability to target multiple genes simultaneously. However, the application of genome editing remains concentrated in a few model cultivars, and challenges persist in optimizing transformation protocols, minimizing off-target effects, and validating edited traits under field conditions. Future directions involve expanding the genetic base, integrating genome editing with synthetic biology, and addressing regulatory and public acceptance issues. Overall, genome editing offers significant potential for sustainable soybean improvement, supporting food security and agricultural resilience in the face of global challenges. Full article

Prime editing is a promising approach for correcting pathogenic variants, but its efficiency remains variable across genomic contexts. Here, we systematically evaluated 12 modifications of the PEmax system for correcting the CFTR F508del pathogenic variant that caused cystic fibrosis in patient-derived airway basal cells. We chose EXO1 and FEN1 nucleases to improve the original system. While all tested variants showed comparatively low efficiency in this AT-rich genomic region, 4-FEN modification demonstrated significantly improved editing rates (up to 2.13 fold) compared to standard PEmax. Our results highlight two key findings: first, the persistent challenge of AT-rich target sequence correction even with optimized editors, and second, the performance of 4-FEN suggests its potential value for other genomic targets. Full article

Plant architecture is a crucial agronomic trait significantly impacting soybean (Glycine max) yield. Traditional breeding has made some progress in optimizing soybean architecture, but it is limited in precision and efficiency. The Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein (CRISPR/Cas) system, a revolutionary gene-editing technology, provides unprecedented opportunities for plant genetic improvement. This review outlines CRISPR’s development and applications in crop improvement, focusing specifically on progress regulating soybean architecture traits affecting yield, such as node number, internode length, branching, and leaf morphology. It also discusses the technical challenges for CRISPR technology in enhancing soybean architecture, including that the regulatory network of soybean plant architecture is complex and the development of multi-omics platforms helps gene mining. The application of CRISPR enables precise the regulation of gene expression through promoter editing. Meanwhile, it is also faced with technical challenges such as the editing of homologous genes caused by genome polyploidy, the efficiency of editing tools and off-target effects, and low transformation efficiency. New delivery systems such as virus-induced genome editing bring hope for solving some of these problems. The review emphasizes the great potential of CRISPR technology in breeding next-generation soybean varieties with optimized architecture to boost yield potential. Full article

Prime editing (PE), a novel “search-and-replace” genome editing technology, demonstrates significant potential for crop genetic improvement due to its precision and versatility. However, since its initial application in plants, PE technology has consistently faced challenges of low and variable editing efficiency, representing a major bottleneck hindering its broader application. Therefore, this study conducted a systematic review following the PRISMA 2020 guidelines. We systematically searched databases—Web of Science, PubMed, and Google Scholar—for studies published up to June 2025 focusing on enhancing PE performance in crops. After a rigorous screening process, 38 eligible primary research articles were ultimately included for comprehensive analysis. Our analysis revealed that early PE systems such as PE2 could perform diverse edits, including all 12 base substitutions and small insertions or deletions (indels), but their efficiency was highly variable across species, targets, and edit types. To overcome this bottleneck, researchers developed four major optimization strategies: (1) engineering core components such as Cas9, reverse transcriptase (RT), and editor architecture; (2) enhancing expression and delivery via optimized promoters and vectors; (3) improving reaction processes by modulating DNA repair pathways or external conditions; and (4) enriching edited events through selectable or visual markers. These advancements broadened PE’s targeting scope with novel Cas9 variants and enabled complex, kilobase-scale DNA insertions and rearrangements. The application of PE technology in plants has evolved from basic functional validation, through systematic optimization for enhanced efficiency, to advanced stages of functional expansion. This review charts this trajectory and clarifies the key strategies driving these advancements. We posit that future breakthroughs will increasingly depend on synergistically integrating these strategies to enable the efficient, precise, and predictable application of PE technology across diverse crops and complex breeding objectives. This study provides an important theoretical framework and practical guidance for subsequent research and application in this field. Full article

Hippophae rhamnoides ssp. sinensis Rousi a species of significant ecological and economic value that is native to the Qinghai–Tibet Plateau and arid/semi-arid regions. Investigating the mitochondrial genome can elucidate stress adaptation mechanisms, population genetic structure, and hybrid evolutionary history, offering molecular insights for ecological restoration and species conservation. However, the genetic information and evolutionary mechanisms of its mitochondrial genome remain poorly understood. This study aimed to assemble the complete mitochondrial genome of H. rhamnoides L. ssp. sinensis using Illumina sequencing, uncovering its structural features, evolutionary pressures, and environmental adaptability and addressing the research gap regarding mitochondrial genomes within the Hippophae genus. The study assembled a 454,444 bp circular mitochondrial genome of H. rhamnoides ssp. sinensis, with a GC content of 44.86%. A total of 73 genes and 3 pseudogenes were annotated, with the notable absence of the rps2 gene, which is present in related species. The genome exhibits significant codon usage bias, particularly with high-frequency use of the alanine codon GCU and the isoleucine codon AUU. Additionally, 449 repetitive sequences, potentially driving genome recombination, were identified. Our evolutionary pressure analysis revealed that most genes are under purifying selection, while genes such as atp4 and nad4 exhibit positive selection. A nucleotide diversity analysis revealed that the sdh4 gene exhibits the highest variation, whereas rrn5 is the most conserved. Meanwhile, phylogenetic analysis showed that H. rhamnoides ssp. sinensis from China is most closely related to Hippophae tibetana, with extensive homologous sequences (49.72% of the chloroplast genome) being identified between the chloroplast and mitochondrial genomes, indicating active inter-organellar gene transfer. Furthermore, 539 RNA editing sites, primarily involving hydrophilic-to-hydrophobic amino acid conversions, were predicted, potentially regulating mitochondrial protein function. Our findings establish a foundation for genetic improvement and research on adaptive evolutionary mechanisms in the Hippophae genus, offering a novel case study for plant mitochondrial genome evolution theory. Full article

Plants must contend with oxidative stress, a paradoxical phenomenon in which reactive oxygen species (ROS) can cause cellular damage while also serving as key signaling molecules. Environmental stressors, such as drought, salinity, and temperature extremes, promote ROS accumulation, affecting plant growth and productivity. To maintain redox homeostasis, plants rely on antioxidant systems comprising enzymatic defenses, such as superoxide dismutase, catalase, and ascorbate peroxidase, and non-enzymatic molecules, including ascorbate, glutathione, flavonoids, and emerging compounds such as proline and nano-silicon. This review provides an integrated overview of antioxidant responses and their modulation through recent biotechnological advances, emphasizing the role of emerging technologies in advancing our understanding of redox regulation and translating molecular insights into stress-resilient phenotypes. Omics approaches have enabled the identification of redox-related genes, while genome editing tools, particularly those based on clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, offer opportunities for precise functional manipulation. Artificial intelligence and systems biology are accelerating the discovery of regulatory modules and enabling predictive modeling of antioxidant networks. We also highlight the contribution of synthetic biology to the development of stress-responsive gene circuits and address current regulatory and ethical considerations. Overall, this review aims to provide a comprehensive perspective on molecular, biochemical, and technological strategies to enhance oxidative stress tolerance in plants, thereby contributing to sustainable agriculture and food security in a changing climate. Full article

Background and Objectives: Over the past few years, there has been a significant shift in focus from developing better diagnostic tools to detecting Alzheimer’s disease (AD) earlier and initiating treatment interventions. This review will explore four main objectives: (a) the role of biomarkers in enhancing the diagnostic accuracy of AD, highlighting the major strides that have been made in recent years; (b) the role of neuropsychological testing in identifying biomarkers of AD, including the relationship between cognitive performance and neuroimaging biomarkers; (c) the amyloid hypothesis and possible molecular mechanisms of AD; and (d) the innovative AD therapeutics and the challenges and limitations of AD research. Materials and Methods: We have searched PubMed and Scopus databases for peer-reviewed research articles published in English (preclinical and clinical studies as well as relevant reviews and meta-analyses) investigating the molecular mechanisms, biomarkers, and treatments of AD. Results: Genome-wide association studies (GWASs) discovered 37 loci associated with AD risk. Core 1 biomarkers (α-amyloid Aβ42, phosphorylated tau, and amyloid PET) detect early AD phases, identifying both symptomatic and asymptomatic individuals, while core 2 biomarkers inform the short-term progression risk in individuals without symptoms. The recurrent failures of Aβ-targeted clinical studies undermine the amyloid cascade hypothesis and the objectives of AD medication development. The molecular mechanisms of AD include the accumulation of amyloid plaques and tau protein, vascular dysfunction, neuroinflammation, oxidative stress, and lipid metabolism dysregulation. Significant advancements in drug delivery technologies, such as focused Low-Ultrasound Stem, T cells, exosomes, nanoparticles, transferin, nicotinic and acetylcholine receptors, and glutathione transporters, are aimed at overcoming the BBB to enhance treatment efficacy for AD. Aducanumab and Lecanemab are IgG1 monoclonal antibodies that retard the progression of AD. BACE inhibitors have been explored as a therapeutic strategy for AD. Gene therapies targeting APOE using the CRISPR/Cas9 genome-editing system are another therapeutic avenue. Conclusions: Classic neurodegenerative biomarkers have emerged as powerful tools for enhancing the diagnostic accuracy of AD. Despite the supporting evidence, the amyloid hypothesis has several unresolved issues. Novel monoclonal antibodies may halt the AD course. Advances in delivery systems across the BBB are promising for the efficacy of AD treatments. Full article

Powdery mildew, predominantly caused by Podosphaera xanthii and Golovinomyces orontii, presents a major constraint to cucurbitaceous crop production worldwide. Despite intensive research, the complex interplay between pathogen virulence factors and host immune responses remains only partially understood. Recent advances in genomics, transcriptomics, and gene editing technologies have shed light on key molecular mechanisms underlying host susceptibility, quantitative resistance, and potential durable control strategies. In this review, we summarize the biology of powdery mildew fungi infecting cucurbits, the latest findings on pathogen effectors, plant defense signaling, and the genetic basis of resistance. We also discuss novel breeding and biotechnological approaches for durable powdery mildew resistance and outline future directions for integrative disease management strategies. Full article

Systemic light-chain (AL) amyloidosis is a challenging, complex and heterogeneous disease. AL amyloidosis is classified under the category of plasma cell neoplasms and other diseases with paraproteins in the fifth edition of the World Health Organization classification of lymphoid tumors. Epidemiological information is limited, largely due to its low incidence and the lack of a global network of population-based specific registries. Despite recent advances, AL amyloidosis is still considered an incurable disease. The presence of a precursor disease, particularly monoclonal gammopathy of uncertain significance, is the main consolidated risk factor. Limited knowledge about other risk factors precludes the possibility of establishing preventive measures. A relevant percentage of AL amyloidosis patients fulfill the current diagnostic criteria of multiple myeloma. Incidence should be evaluated in the setting of population-based studies. On the one hand, incidence shows a slightly increasing pattern. On the other hand, survival is progressively increasing. Consequently, prevalence is also rising. Early mortality, commonly associated with advanced heart involvement, remains a serious drawback to improve the outcome. Epidemiology represents the first level of heterogeneity in AL amyloidosis. Both genomic and clinical epidemiological research in systemic AL amyloidosis have a crucial role in the global strategy to combat this multifaceted disease. Full article

Background: Centella asiatica, a medicinally important species that is rich in bioactive compounds, lacks a characterized mitochondrial genome, despite nuclear and chloroplast assemblies. We sequenced and annotated its mitochondrial genome to elucidate its genetic foundations and evolutionary mechanisms. Methods: Assembly using Illumina short-reads and Nanopore long-reads was used to characterize the mitochondrial genome. Analyses included structural characterization, codon usage bias, repetitive sequences, horizontal gene transfer (HGT), collinearity, and phylogeny. The resulting tissue-specific (root, stem, and leaf) long non-coding RNA (lncRNA) profiles identified RNA editing sites. Results: The complete mitochondrial genome (249,777 bp, 45.5% GC) comprises three circular contigs encoding 51 genes (33 protein-coding, 15 tRNA, and 3 rRNA). Comparative genomics revealed synteny with the Apiaceae family of plants and evidence of HGT. Phylogenetic analysis resolved taxonomic relationships within Apiales. We predicted that 547 RNA editing sites would be identified in its protein-coding genes. Tissue profiling identified 725 (root), 711 (stem), and 668 (leaf) editing sites, with >71% concordance to predictions. RNA editing-generated cryptic promoters/terminators occur in mitochondrial core function genes (e.g., ATP synthase, cytochrome c reductase/oxidase, ribosome large subunit, and cytochrome c biogenesis), exhibiting a lower frequency in the leaves compared to the roots and stems. Conclusions: We provide the first complete mitochondrial genome assembly for C. asiatica, delineating its complex structure, tissue-modulated RNA editing, and evolutionary trajectory. This high-quality genomic resource establishes a foundation for molecular evolutionary studies and enhances the genomic toolkit for this pharmacologically significant species. Full article

Transposable elements (TEs) serve as important drivers mediating polyploidization events and phenotypic diversification in plant genomes. However, the dynamic changes in various TE subclasses post-polyploidization and their mechanisms of influencing phenotypic variation require further investigation. The allopolyploid Gossypium species, originating from two diploid progenitors, provide an ideal model for studying TE dynamics following polyploidization. This study investigated TE dynamics post-polyploidization based on 21 diploid and 7 polyploid cotton genomes. The Tekay subclass of the Gypsy serves as a major driver of Gossypium genome evolution, as it underwent two burst events in the At-subgenome and its progenitor, exhibiting the highest abundance, longest length, and largest proportion among all TE subclasses. In contrast, the Gopia superfamily Tork subclass has lower abundance but greater genic association, facilitating environmental adaptation and phenotypic variation. Additionally, a pan-TE-related structural variation, the pan-TRV map, was constructed by integrating resequencing data from 256 accessions. Genome-wide analysis of 28 cotton genomes identified 142,802 TRVs, among which 72,116 showed polymorphisms in the 256 G. hirsutum accessions. The Gypsy superfamily, particularly the Tekay subclass, has been identified as a major source of TRVs, while Copia-type elements demonstrate significantly greater enrichment in gene-proximal genomic regions. A total of 334 TRVs exhibiting statistically significant associations with 10 key phenotypic traits, including 164 TRVs affecting yield components and 170 TRVs determining fiber quality. This investigation delineates the evolutionary significance of transposable elements in Gossypium genome diversification while simultaneously providing novel functional markers and potential editing targets for genetic dissection and molecular breeding of key agronomic traits in cotton. Full article

Multidrug resistance (MDR) remains a formidable barrier to successful cancer treatment, driven by mechanisms such as efflux pump overexpression, enhanced DNA repair, evasion of apoptosis and the protective characteristics of the tumour microenvironment. Nanoparticle-based delivery systems have emerged as promising platforms capable of addressing these challenges by enhancing intracellular drug accumulation, enabling targeted delivery and facilitating stimuli-responsive and controlled release. This review provides a comprehensive overview of the molecular and cellular mechanisms underlying MDR and critically examines recent advances in nanoparticle strategies developed to overcome it. Various nanoparticle designs are analysed in terms of their structural and functional features, including surface modifications, active targeting ligands and responsiveness to tumour-specific cues. Particular emphasis is placed on the co-delivery of chemotherapeutic agents with gene regulators, such as siRNA, and the use of nanoparticles to deliver CRISPR/Cas9 gene editing tools as a means of re-sensitising resistant cancer cells. While significant progress has been made in preclinical settings, challenges such as tumour heterogeneity, limited clinical translation and immune clearance remain. Future directions include the integration of precision nanomedicine, scalable manufacturing and non-viral genome editing platforms. Collectively, nanoparticle-based drug delivery systems offer a multifaceted approach to combat MDR and hold great promise for improving therapeutic outcomes in resistant cancers. Full article

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive photoreceptor cell loss leading to irreversible vision loss. Affecting approximately 1 in 4000 individuals worldwide, retinitis pigmentosa exhibits significant genetic heterogeneity, with mutations in genes such as RHO, PRPF31, RPE65, USH2A, and NR2E3, which contribute to its diverse clinical presentation. This review outlines the genetic basis of retinitis pigmentosa and explores cutting-edge gene-based therapeutic strategies. Luxturna (voretigene neparvovec-rzyl), the first FDA-approved gene therapy targeting RPE65 mutations, represents a milestone in precision ophthalmology, while OCU400 is a gene-independent therapy that uses a modified NR2E3 construct to modulate retinal homeostasis across different RP genotypes. Additionally, CRISPR–Cas genome-editing technologies offer future potential for the personalized correction of specific mutations, though concerns about off-target effects and delivery challenges remain. The article also highlights MCO-010, a novel optogenetic therapy that bypasses defective phototransduction pathways, showing promise for patients regardless of their genetic profile. Moreover, QR-1123, a mutation-specific antisense oligonucleotide targeting the P23H variant in the RHO gene, is under clinical investigation for autosomal dominant RP and has shown encouraging preclinical results in reducing toxic protein accumulation and preserving photoreceptors. SPVN06, another promising candidate, is a mutation-agnostic gene therapy delivering RdCVF and RdCVFL via AAV to support cone viability and delay degeneration, currently being evaluated in a multicenter Phase I/II trial for patients with various rod–cone dystrophies. Collectively, these advances illustrate the transition from symptom management toward targeted, mutation-specific therapies, marking a major advancement in the treatment of RP and inherited retinal diseases. Full article