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PubMed2026

Inducible flocculation in Komagataella phaffii enables enhanced biomass separation for biopharmaceutical production.

Biomass separation represents a critical bottleneck in Komagataella phaffii-based biopharmaceutical processes, as typically high cell densities of 40 - 50 % create significant operational, technical and economic challenges for harvest operations. Yeast cell aggregation (flocculation) provides a solution to accelerate cell sedimentation by increasing particle size, thus allowing to improve biomass-supernatant separation efficiency during both natural gravity settling and (continuous) centrifugation operations. This study demonstrates successful engineering of K. phaffii strains with an inducible flocculation phenotype using CRISPR/Cas9-based genome editing to integrate the Saccharomyces cerevisiae FLO1 (ScFLO1) gene under control of various regulatory elements, including methanol-inducible and derepressible promoters. Flocculation strength could be enhanced by implementing transcriptional positive feedback circuits based on the methanol-inducible AOX1 promoter. To address methanol-free production requirements, we developed alternative systems to retrofit PAOX1-based ScFLO1 expression and exploited the derepressible PDF promoter, offering broader compatibility with biopharmaceutical manufacturing facilities. Flocculating cells cultivated in a bioreactor demonstrated significantly improved sedimentation behavior, with considerably lower supernatant turbidity after short low-speed centrifugation or gravity sedimentation compared to non-flocculating controls. Crucially, cell flocculation had no negative impact on product amount and quality when expressing a multivalent NANOBODY® VHH molecule with pharmaceutical relevance. Thus, this work establishes the first genetically engineered flocculation system in K. phaffii compatible with recombinant protein production, providing the basis for an innovative approach to streamline harvest operations in biopharmaceutical processes.

Flocculation↗

PubMed2026

Ligand-Mediated Reprogramming Redirects Liver-Tropic Ionizable Lipid Nanoparticles for Lung-Selective mRNA Delivery.

Systemic delivery of messenger RNA (mRNA) to target tissues and cells using lipid nanoparticles (LNPs) holds transformative potential for gene therapy. However, most clinically validated LNP exhibit strong liver tropism, and redirecting their organ specificity without redesigning entirely new chemistries remains challenging. Here we present a ligand-mediated lipid reprogramming approach that repurposes chemically defined, liver-tropic, ionizable lipids (lipidoids) for mRNA delivery beyond the liver. From a library of 90 degradable lipidoids, we identified 2-t6b as a potent liver-targeting platform. By site-specific displaying of small molecule ligands onto 2-t6b headgroup, we engineered a series of reconfigured lipidoids that achieve lung-specific targeting while retaining the parent delivery scaffold. Ligand7-2-t6b-lipid-functionalized LNP achieved over 200-fold higher mRNA translation in the lungs compared to the parent liver-tropic LNP. Proteomics and molecular docking analysis revealed enhanced binding of the modified lipid to vitronectin, a serum glycoprotein that improves integrin binding and thus promotes cellular uptake and translation efficiency. Ligand-mediated 2-t6b/ligand7 LNPs achieved outperformed efficacy and therapeutic potential in lung-specific genome editing relative to SORT-constructed 2-t6b LNP system. Our modular reprogramming strategy provides a generalizable framework to upgrade existing liver-biased LNPs into lung-selective mRNA carriers, advancing next-generation tissue-specific mRNA therapies for gene editing, protein replacement therapy, and regenerative medicine.

RNA, Messenger↗

PubMed2024

Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

OBJECTIVE: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex. METHODS: The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and immunoaffinity-purified anti-PDGFRα antibodies from sera of patients with SSc. RESULTS: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P < 0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls. CONCLUSION: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

Humans↗

PubMed2026

Nanocarrier-Based Gene Delivery Systems: Mechanisms, Clinical Translation, and Future Perspectives.

Gene therapy holds revolutionary potential for managing genetic disorders, cancers and infectious illnesses. However, one of the biggest challenges is delivering DNA or RNA into targeted cells and in the safe and effective way. In this review, nano carrier-based approaches for gene delivery are critically examined, focusing on both viral and non-viral systems. The advancement of CRISPR-Cas genome editing, machine learning-assisted nanocarrier optimization, and biologically inspired delivery systems is being quickly pushed forward in this area. In this review, a comparative analysis of gene delivery systems is being provided, and the key challenges to clinical translation are being pointed out. In addition, expert opinions on future research directions are being offered, with a heavy focus on the development of multifunctional, precisely targeted, and easily scalable delivery systems that can be integrated with next-generation therapeutic technologies.

Humans↗

PubMed2026

A predator-derived odor specifically triggers avoidance in gregarious mated female Locusta migratoria.

BACKGROUND: Insects possess a highly specialized olfactory system. The migratory locust (Locusta migratoria), a major agricultural pest, is thought to emit odors that serve as aposematic signals to protect gregarious individuals from predation. However, whether locusts can detect the odors of their natural enemies to preemptively avoid predation remains unclear. RESULTS: Here, we show that gregarious mated female locusts exhibit strong avoidance behavior toward the odors of two avian predators, Numida meleagris and Anas platyrhynchos. Through volatile compound profiling, we identified 1-octen-3-ol, a key predator-released odor, which elicited significant aversive responses specifically in gregarious mated females; notably, virgin females showed no behavioral response to this odor. Through screening 82 olfactory receptors in L. migratoria, we identified two receptors, LmOR1 and LmOR17, that detect 1-octen-3-ol. A temporal expression study of LmOR1 and LmOR17 across different developmental stages of two locust phases using quantitative real-time polymerase chain reaction (qRT-PCR) showed that both genes are significantly more highly expressed in the gregarious mated females. Genome editing of these receptors revealed that knockout of LmOR1 significantly reduced both the electrophysiological response and the behavioral avoidance of 1-octen-3-ol, whereas knockout of LmOR17 had no effect. In our results we thus uncover a striking mating-state dependence of an innate avoidance behavior to a predator-derived odor, and further we identify LmOR1 as the major receptor mediating this olfactory-driven defense. CONCLUSION: Our findings provide crucial insights into the behavioral and olfactory mechanisms underlying insect-predator interactions, as well as the role of mating status in modulating defensive responses, offering potential olfactory targets for locust management. © 2026 Society of Chemical Industry.

Animals↗

PubMed2025

Minimal Perturbation Analysis of mRNA Degradation Rates with Tet-Off and RT-qPCR.

Messenger RNA stability is an important variable in gene expression and its dynamics. High stability ensures a constant level of synthesized protein, whereas mRNA instability can be critical for regulatory processes in which protein production needs to be stopped, such as development, inflammation, or adaptation to stress. Accurate measurements of RNA degradation rates are important for understanding how RNA features and RNA binding proteins affect the posttranscriptional life of an mRNA. As an alternative to global transcriptional inhibition methods, the use of a Tet-off repressible promoter has the advantage that cells are minimally perturbed by the addition of doxycyclin during the assay. We illustrate the use of a reporter mRNA expressed from a plasmid in Saccharomyces cerevisiae cells, but similar methods can be applied to other regulated promoters, on plasmids or by genome editing, and in other organisms. RNA levels are measured by reverse transcription followed by quantitative PCR. An exponential decay law is then used to estimate how well the measurements follow this expected trend for the simplest possible mechanism of RNA degradation, where the decay is proportional to the amount of RNA present at any given time.

RNA Stability↗

PubMed2025

SelectRepair Knockout: Efficient PTC-Free Gene Knockout Through Selectable Homology-Directed DNA Repair.

Generating nonessential gene knockouts using CRISPR/Cas9 technology is becoming increasingly common in biological research. In a typical workflow, the Cas9 endonuclease is used to induce a DNA double-strand break that relies on nonhomologous end-joining (NHEJ) to introduce a premature termination codon (PTC) in the target gene. The goal is to isolate clones in which the gene produces PTC-containing mRNA transcripts that are degraded via nonsense-mediated mRNA decay (NMD) to cause loss of gene function. Unfortunately, this approach is laborious, and not all PTCs trigger NMD. More importantly, mounting evidence suggest that PTC mutations can also result in a transcriptional adaptation response that can mask the effects of a PTC-mediated gene knockout. In this chapter, we present a PTC-free gene knockout strategy that implements homology-directed DNA repair (HDR) with selectable markers to substantially reduce the complexity of the screening and validation of genome edits in cells containing more than one gene copy as in the case of the commonly used hypotriploid HEK293 cell line. We describe how to obtain a complete knockout of the Ligase IV protein (LIG4) and provide considerations for the application of this SelectRepair Knockout method to other genes.

Humans↗

PubMed2025

CRISPR/Cas9-Mediated Gene-Knockout and In Situ Complementation System for Phytophthora sojae.

The establishment of reliable and efficient systems for genome editing in Phytophthora is very important for studying gene functions. Here, step-by-step methods for CRISPR/Cas9-based gene knockout and in situ complementation for Phytophthora sojae are presented. These steps include the sgRNA design, Cas9-sgRNA plasmid construction, homologous replacement, complementation vector construction, P. sojae transformation, and detection of mutations for both gene knockout and in situ complementation. These methods may also potentially be adapted for other Phytophthora species.

Phytophthora↗

PubMed2025

Harnessing primary, secondary and tertiary genepools for durable wheat disease resistance.

Bread wheat (Triticum aestivum), a cornerstone of global food security contributing ~ 20% of daily caloric intake, faces increasing vulnerability to rapidly evolving pathogens. This is due in part to a narrowed genetic base following domestication and modern breeding. Wild and ancestral wheat relatives are critical reservoirs of disease resistance genes for breeding new, resilient varieties. This review explores the contributions of primary, secondary, and tertiary genepools of wheat to disease resistance, highlighting loci effective against fungal pathogens that threaten European wheat production. It examines the challenges of alien gene transfer including crossability barriers, hybrid necrosis, and suppressor loci and reviews modern breeding tools such as marker-assisted selection, genomic selection, and genome editing for harnessing exotic germplasm. By synthesising current knowledge, this review highlights the vital contribution of ancestral wheat germplasm in enhancing the resilience and productivity of future wheat crops against increasing biotic stresses.

Triticum↗

PubMed2026

Transforming Plant Viruses into Vectors for Next-Generation Agriculture-A Review.

Plant viral vectors have evolved from tools for transient gene expression into a versatile platform for precise genetic intervention, offering a rapid, transgene-free alternative to conventional crop transformation. This review critically assesses their engineering for scalable field application, moving beyond foundational techniques like virus-induced gene silencing (VIGS). We highlight how advanced vector design, including deconstructed genomes and synthetic regulatory circuits enhances cargo capacity, specificity, and biosafety. The integration of viral delivery with CRISPR-Cas systems has unlocked virus-induced genome editing (VIGE), base editing, and prime editing, enabling heritable trait modification without tissue culture. However, the transition from proof-of-concept in model plants to robust field technology hinges on overcoming critical bottlenecks: expanding host range through chimeric vectors, ensuring environmental containment, and developing scalable delivery methods such as nano-formulations or adjusted agroinfiltration protocols. We evaluate these delivery routes and emerging synergies with nanobiotechnology for targeted and efficient applications. While challenges in regulation, public perception, and large-scale production persist, the strategic engineering of viral vectors for stability, specificity, and safety positions them as a transformative, next-generation biotechnological input for achieving sustainable crop improvement and protection under changing climatic conditions.

Plant Viruses↗

PubMed2026

Allelochemical signaling and phytohormone crosstalk in plants: molecular mechanisms and implications for sustainable weed management.

Phytotoxic effects from allelopathy occur due to signaling pathways that induce alterations in hormonal balance within the plants, thereby hindering weed growth. Signaling crosstalk between various hormones and signaling pathways (Ca2⁺, MAPK, ROS) is involved in the molecular response mechanisms found through omics. Utilizing such mechanisms would help develop new environmentally friendly methods for sustainable weed management. Allelopathy serves as an essential component of plant-plant interaction via controlling the secretion of secondary metabolites (allelochemicals), which affect the growth, development, and physiological activity of nearby plants. The latest findings indicate that allelochemicals disturb phytohormone balance and signaling pathways resulting in oxidative stress, metabolism dysfunctions, cellular processes disturbances, and eventually inhibiting the growth of target weed species. Molecular biology progress and omics techniques brought information about the sophisticated regulation processes involved in allelopathic interactions. This review summarizes the information about the molecular mechanism of weed suppression mediated by allelopathy with the emphasis on allelochemical perception, phytohormone signaling, ROS responses, and evidence obtained by the application of transcriptomics, proteomics, metabolomics, and other omics-based studies. In addition, it introduces novel approaches, such as rhizosphere engineering, nanotechnologies, and genome editing, which may improve the effectiveness and reliability of allelopathic weed suppression. Overall, these achievements provide prospects for creating a new generation of weed control technologies that are sustainable, environmentally friendly, and climate-adaptive.

Plant Growth Regulators↗

PubMed2026

Transgenic overexpression of GmAPC7-CT improves seed yield and reduces susceptibility to soybean mosaic virus and Meloidogyne incognita in soybean.

Stable transgenic soybean lines overexpressing the GmAPC7-CT gene have demonstrated increased seed yield and reduced susceptibility to the soybean mosaic virus and Meloidogyne incognita. The Anaphase-Promoting Complex subunit 7 (APC7) is a core structural component of the anaphase-promoting complex or cyclosome (APC/C). The terminal region of this AtAPC7 gene has been shown in Arabidopsis thaliana to accumulate more transcripts than the full-length gene. The AtAPC7-CT gene (terminal region of the AtAPC7) encodes a protein with significant homology to a tobacco viral replication inhibitor (IVR). Its stable overexpression in transgenic A. thaliana lines resulted in notable improvements in biomass, seed yield, earliness of vegetative-reproductive transitions, and reduced susceptibility to viruses. In this study, we generated stable transgenic soybean lines overexpressing the GmAPC7-CT gene (terminal region or 3' portion of Glyma.15G096000, corresponding to the AtAPC7-CT) and evaluated seed yield and susceptibility of these lines to soybean mosaic virus and Meloidogyne incognita. The GmAPC7-CT gene is 624 nucleotides long and encodes a 207-amino acid protein with two tetratricopeptide repeat (TPR) domains. GmAPC7-CT showed 100% amino acid identity with full-length GmAPC7, 81.16% identity with AtAPC7-CT, and 87.94% identity with tobacco IVR. Stable transgenic lines demonstrated significant advancements in plant development and seed yield, with the top three lines producing up to 43% more pods, 44% more seeds, and a 16% increase in seed weight. Furthermore, these soybean lines showed up to a 70% reduction in susceptibility to soybean mosaic virus and M. incognita, reflected by decreased viral RNA load and nematode reproduction factor. Collectively, these results support a conserved role of GmAPC7-CT in soybean and AtAPC7-CT in A. thaliana, acting similarly to the tobacco IVR. Thus, our findings underscore the strong biotechnological potential of the GmAPC7-CT gene to improve key agronomic traits in soybean through genetic engineering approaches, including conventional breeding, transgenesis, and genome editing.

Glycine max↗

PubMed2026

Seed shattering habit in millets and the secrets of the abscission layer - a comprehensive review.

Though seed shattering continues to be a significant barrier affecting yield stability and harvesting efficiency in millets and other grasses, millets are increasingly acknowledged as climate-resilient, nutrient-rich 2007cereal crops with the potential to strengthen global nutritional and food security under the combined pressures of climate change, population growth, and limited natural resources. Since strong artificial selection favoured non-shattering phenotypes during domestication, seed shattering, an adaptive trait in wild species that promotes seed dispersal through the formation and activation of specialised abscission layers, became a distinguishing feature of cultivated cereals. With a focus on the morphological, physiological, hormonal, and genetic modulation of the abscission zone, this article summarizes the state of the art regarding seed shattering in millets. Abscission layer morphology, location, and lignification vary greatly among grasses, from well-defined lignified zones in rice and sorghum to non-lignified and anatomically subtle zones in Setaria and Panicum species. Cell wall-modifying enzymes like polygalacturonases, cellulases, expansins, and pectin methylesterases that mediate middle lamella degradation are modulated by coordinated hormonal signalling involving auxin, ethylene, and abscisic acid, which controls the timing and progression of cell separation at the physiological level. Domestication-related genes, including SH1, qSH1, SH4, and LES1, demonstrate convergent evolutionary mechanisms controlling abscission layer development in a variety of grass lineages at the molecular level. Understanding these regulatory networks has been greatly enhanced by recent developments in transcriptomics, functional genomics, and genome sequencing in both model species and underused millets. The role of millets as climate-smart cereals for sustainable future agriculture is reinforced by the integration of anatomical, physiological, and genetic insights, which offer a solid basis for targeted breeding and genome-editing strategies intended to improve seed retention, enhance yield stability, and increase harvest efficiency.

Abscission Layer↗

PubMed2026

Integrated transcriptomic and metabolomic analysis reveals candidate regulatory networks associated with starch accumulation in tetraploid potato.

Potato (Solanum tuberosum L.) tuber starch is a major determinant of crop quality and industrial value, yet the regulatory mechanisms underlying starch accumulation in autotetraploid cultivars remain poorly resolved. Here, we performed integrated transcriptomic and metabolomic analyses using a segregating tetraploid population derived from parents with contrasting starch content. Extreme phenotypes were selected to systematically dissect the molecular basis of starch accumulation. Transcriptome profiling revealed extensive transcriptional reprogramming between high- and low-starch genotypes, with differentially expressed genes significantly enriched in carbohydrate metabolism, particularly the starch and sucrose metabolism pathway. Notably, multiple transcription factor families, including AP2/ERF, MYB, and bHLH, were prominently represented, suggesting coordinated regulatory control. Metabolomic analysis identified substantial metabolic divergence, with differentially accumulated metabolites predominantly enriched in starch and sucrose metabolism as well as secondary metabolic pathways. Most metabolites exhibited negative associations with starch content, indicating competitive carbon allocation between primary and secondary metabolism. Integrative multi-omics analysis further resolved a core regulatory module comprising key structural genes and transcription factors tightly associated with starch-related metabolites. In particular, genes involved in sucrose cleavage and ADP-glucose metabolism, together with trehalose-6-phosphate synthase (TPS) and UDP-glucose-associated pathways, emerged as critical nodes linking carbon flux to starch biosynthesis. Correlation network analysis suggested that AP2/ERF-, MYB-, and bHLH-type transcription factors modulate these pathways by coordinating structural gene expression and metabolic flux distribution. Collectively, our study establishes a transcriptional-metabolic framework for starch accumulation in tetraploid potato, highlighting the central role of carbon allocation and signaling intermediates in shaping starch content, and providing candidate targets for molecular breeding and genome editing.

Solanum tuberosum↗

PubMed2025

Loss of responses to odorants and pheromones in mPRγ (paqr5b)-knockout zebrafish.

In our previous study, we generated a membrane-type progesterone receptor γ (paqr5b) knockout zebrafish line. Knocking out paqr5b by genome editing resulted in the loss of neurons in the olfactory rosette (OR). These findings indicated that Paqr5b plays an essential role in the formation of olfactory neurons. In this study, we investigated the extent to which paqr5b-/- fish lacking olfactory neurons retain their sense of smell. We used a reported tank for zebrafish olfactory analysis with a dividing plate in the middle. The tank was divided into three zones: the right zone, where test substances were added; the neutral zone; and the left zone. The fish were released into the neutral zone at the beginning of each test, the chemical was added to the corner of the right zone, and a 3-min video was taken to track the movements of the fish. The video was then played back, and the time spent in the three zones was counted manually. Both male and female paqr5b+/+ and paqr5b-/- zebrafish were separately analyzed for time spent in the three zones after exposure to ATP, cadaverine, and the pheromone 17α,20β-dihydroxy-4-pregnen-3-one (DHP). Both male and female paqr5b+/+ zebrafish were strongly attracted to ATP and stayed in the right zone for approximately 2 min (67%). In addition, paqr5b+/+ zebrafish avoided cadaverine and stayed longer in the left zone than in any other zone. In contrast, paqr5b-/- zebrafish stayed in all three zones for approximately the same amount of time, even after exposure to ATP and cadaverine. The paqr5b+/+ fish were attracted to DHP and stayed in the right zone longer. Paqr5b-/- zebrafish of either sex were not reactive to DHP exposure. These results showed that paqr5b-/- zebrafish lacking olfactory neurons lost responsiveness to odorants and pheromones.

Animals↗

PubMed2026

Zebrafish as a versatile model in biomedical research, from disease modeling to regenerative medicine: a review.

Zebrafish are an effective animal model widely utilized in biomedical research. They are known for their rapid reproduction and substantial genetic similarity to humans. Their transparent embryos directly enable the visualization of developmental processes and disease progression. This makes zebrafish invaluable for studying a broad range of human diseases, including cancer, cardiovascular disorders, and neurodegenerative conditions. Compared with other vertebrate models, zebrafish offer several advantages, including ease of genome editing, cost-effective maintenance, and suitability for high-throughput drug screening. Recent advancements have expanded the use of zebrafish in disease modeling and regenerative medicine, providing deeper insights into the genetic and cellular mechanisms underlying human pathologies. Zebrafish provide a robust platform for evaluating the safety, efficacy, and regenerative potential of both natural and synthetic biomaterials, including hydroxyapatite, bioactive glass nanoparticles, and bioceramics. This capability facilitates the creation of artificial tissues that closely resemble native structures. Additionally, integrating artificial intelligence technologies has improved automated data analysis and phenotyping in zebrafish studies, enhancing both accuracy and throughput. This review highlights current applications of zebrafish in disease modeling, drug discovery, regenerative medicine, and biomaterial assessment, emphasizing their evolving role as a versatile preclinical platform supported by advanced genetic and computational tools.

Animals↗

PubMed2025

Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling.

PURPOSE: Type I interferonopathy encompasses disorders marked by systemic inflammation and neurological involvement, arising from genetic mutations that result in the upregulation of type I IFN signaling through various mechanisms. Currently, therapeutic options are limited, and no standard therapy exists. This study aims to develop a strategy for identifying new therapeutic targets for type I interferonopathy using induced pluripotent stem cells (iPSCs). METHODS: The IFIH1 R779H variant was introduced into iPSCs through genome editing. RNA sequencing of iPSC-derived dendritic cells (DCs) was performed, and differentially expressed genes (DEGs) were identified. IFN-α secretion, reactive oxygen species (ROS), and mitochondrial oxygen consumption rate (OCR) were analyzed in iPSC-derived DCs. An in silico prediction of compounds binding to the OAS-like domain was conducted. Candidate compounds were evaluated for their ability to inhibit IFN secretion from IFIH1 R779H-mutated iPSC-derived DCs. RESULTS: Transcriptome analysis indicated upregulation of the IFN-related and metabolic pathways. IFIH1 R779H-mutated iPSC-derived DCs exhibited increased OCR and ROS generation, and blocking mitochondrial metabolism significantly reduced excessive IFN-α secretion. Among the DEGs, PML was upregulated, and targeting this gene with arsenic trioxide (ATO), a PML antagonist, suppressed IFN-α secretion from IFIH1 R779H-mutated iPSC-derived DCs. Additionally, bisantrene, phthalylsulfathiazole and ganaplacide were predicted to bind to the RNA binding groove of OAS-like domain of human OASL in silico, effectively inhibiting IFN-α secretion from IFIH1 R779H-mutated DCs. CONCLUSION: Our iPSC-based disease modeling and drug investigation approach provides a robust platform for validating the efficacy and toxicity of candidate therapeutic agents for rare and intractable human diseases such as type I interferonopathy.

Humans↗

PubMed2026

The application of the CRISPR-Cas system in Pseudomonas aeruginosa infections.

Due to the extensive drug resistance of Pseudomonas aeruginosa (P. aeruginosa), it is still a great clinical challenge. The clustered regularly interspaced short palindromic repeats and associated proteins (CRISPR-Cas) system has become a promising strategy against this pathogen. This review critically evaluates the multifaceted applications of CRISPR-Cas technology in P. aeruginosa, including its role in antimicrobial resistance, diagnostics, genome editing, and emerging therapeutic and vaccine strategies. In addition to conducting a comprehensive analysis of various studies, we also compared the performance and limitations of various CRISPR platforms, and discussed the main technologies and transformation obstacles in this field. Finally, we look forward to the direction of applying these experimental tools to clinical research in the future.

Pseudomonas aeruginosa↗