Biology subjects

Zhang, M.

Publications and source records attributed to Zhang, M..

At least 253 records · Page 14Linked to original sources

bioRxiv2025

Housekeeping genes are enriched in rheumatoid arthritis-related genes

Housekeeping genes are often considered to be stably expressed in any tissue, cell, or disease state, and the relationship between housekeeping genes and rheumatoid arthritis (RA) has never been systematically analyzed. Therefore we aimed to explore whether housekeeping genes are abnormally expressed in RA by analyzing 15 datasets that were filtered from 140 gene expression profiles. By cumulative hypergeometric test, for 73.3% (11/15) of the datasets, housekeeping genes were significantly (p < 0.05) enriched in differentially expressed genes (DEGs) between RA patients and healthy controls. Using the relative enrichment factor (Re) as an effect size, a Meta-analysis strategy was adopted to integrate the individual results. The logarithmic Re estimation for multiple studies was 0.48 with the 95% confidence interval ranging from 0.17 to 0.80. The combined effect size was significantly higher than that of the randomized case (p = 0.0012) suggesting a consistent result with the hypergeometric test. The robustness of results was verified by sensitivity and subgroup analyses. Furthermore, the expression fluctuation of housekeeping genes was higher in RA patients than healthy controls and the correlation between DNA methylation and gene expression of housekeeping genes was significantly higher than that of non-housekeeping genes, which indicates the potential epigenetic regulation relationship between housekeeping genes and the pathogenesis of RA. This study identified for the first time a significant enrichment of housekeeping genes in DEGs of RA, which might provide new perspectives for understanding the potential role of housekeeping genes in RA.

bioinformatics↗

bioRxiv2025

Tumor suppressor collateral damage screens reveal mRNA homeostasis protein HBS1L as a novel vulnerability in ch9p21 driven FOCAD deleted cancer

Chromosomal deletion of tumor suppressor genes often occurs in an imprecise manner, leading to co-deletion of neighboring genes. This collateral damage can create novel dependencies specific to the co-deleted context. One notable example is the dependency on PRMT5 activity in tumors with MTAP deletion, which co-occurs with CDKN2A/B loss, leading to the development of MTA-cooperative PRMT5 inhibitors. To identify additional collateral damage context/target pairs for chromosome 9p and other common loci of chromosomal deletions, we conducted a combinatorial CRISPR screen knocking out frequently co-deleted genes in combination with a focused target library. We identified the gene encoding the ribosome rescue factor PELO as synthetic lethal with loss of gene encoding the SKI complex interacting protein FOCAD, which is frequently co-deleted alongside MTAP and CDKN2A/B on chromosome 9p. A genome-wide screen in FOCAD isogenic cells further identified the ribosome rescue GTPase and PELO binding partner HBS1L as the top synthetic lethal target for FOCAD loss. Analysis of publicly available data and genetic manipulation of HBS1L using orthogonal modalities validated this interaction. HBS1L dependency in FOCAD-deleted cells was rescued by FOCAD re-expression, and FOCAD intact cells could be rendered HBS1L-dependent by FOCAD knockout, demonstrating the context specificity of this interaction. Mechanistically, HBS1L loss led to translational arrest and activated the unfolded protein response in FOCAD-deleted cells. In vivo, HBS1L deletion eliminated growth of FOCAD-deleted tumors. Here we propose a model where the FOCAD/SKI complex and HBS1L/PELO work together to resolve aberrant mRNA-induced ribosomal stalling, making the HBS1L/PELO complex an intriguing novel target for treating FOCAD-deleted tumors.

cancer biology↗

bioRxiv2025

IQI: Individualized Quantitative trait loci (QTL) Index

There is currently no standard efficient method to precisely detecting and characterizing the difference of quantitative trait loci (QTL) effect among groups and/or populations at individual level. The main reason is that the traditional global regression based QTL analyses can only derive an overall effect of genetic variants on the quantitative trait in a specific group. It is a big challenge to obtain the individual-level QTL effect, which is necessary for accurate testing and precise characterization. Here, we first proposed an individualized QTL index (IQI) that represents the degree of regulation between genetic variants and the trait for each individual. Based on IQI, Differential QTL (DQ) analysis framework was presented to accurately detect the case-control differences in more detail. In addition, IQI can be a new feature/biomarker applied to various accurate bioinformatics analysis, such as differential analysis, disease prediction, and survival analysis. Overall, IQI affords a new perspective on pathogenic mechanisms and will facilitate the study of genetic regulation more detailedly and precisely.

bioinformatics↗

bioRxiv2025

Enhanced Detection of Glioblastoma Vasculature with Superparamagnetic Iron Oxide Nanoparticles and MRI

Detecting glioblastoma infiltration in the brain is challenging due to limited MRI contrast beyond the enhancing tumour core. This study aims to investigate the potential of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents for improved detection of diffuse brain cancer. We examine the distribution and pharmacokinetics of SPIONs in glioblastoma models with intact and disrupted blood-brain barriers. Using MRI, we imaged RN1-luc and U87MG mice injected with Gadovist and SPIONs, observing differences in blood-brain barrier permeability. Peripheral imaging showed strong uptake of nanoparticles in the liver and spleen, while vascular and renal signals were transient. Susceptibility gradient mapping enabled positive nanoparticle contrast within tumours and provided additional information on tumour angiogenesis. This approach offers a novel method for detecting diffuse brain cancer. Our findings demonstrate that SPIONs enhance glioblastoma detection beyond conventional MRI, providing insights into tumour angiogenesis and opening new avenues for early diagnosis and targeted treatment strategies.

cancer biology↗

bioRxiv2025

Radiation exposure induced blood-brain barrier injury via mitochondria-mediated sterile inflammation

Radiation-induced brain injury (RIBI) is caused by exposure to high doses of ionizing radiation and characterized by severe cognitive dysfunction and brain necrosis. The widespread application of radiotherapy and rapid development of deep space exploration have substantially increased the risk of RIBI. However, the pathogenesis of RIBI is not fully understood, and no effective intervention is available. This work described a blood-brain barrier (BBB) microphysiological system (MPS), that allowed to explore the responses of BBB and distinct brain cells to radiation exposure. This BBB MPS can recapitulate the interface structure and function of BBB in brain microenvironment, including brain endothelial cells, astrocytes, pericytes and microglia co-cultured under flow condition. Following acute exposure to radiation of X-ray or {gamma}-ray, characteristic RIBI-associated pathological responses were observed, including BBB compromise, DNA breaks, inhibited cell proliferation, cell hypertrophy and pro-inflammatory cytokine release. Among the distinctive types of cells, brain endothelial cells showed the highest radiosensitivity as compared to other cells in the MPS. Intriguingly, X-ray and {gamma}-ray radiation consistently induced prominent sterile inflammation responses, especially type I interferon response, in the BBB MPS. These responses were mediated by radiation-induced mitochondrial DNA release and subsequent activation of cGAS-STING signaling pathway. Furthermore, we found abrocitinib (JAK1 inhibitor) and idebenone (mitochondrial protectant) can attenuate radiation-induced inflammation and ameliorate BBB injury. These findings revealed the involvement of mitochondria-mediated inflammation in RIBI pathogenesis, identifying mitochondria as a potential target for new radioprotective measures.

neuroscience↗

bioRxiv2025

Nipah virus matrix protein utilizes cortical actin to stabilize the virus assembly sites and promote budding

Several families of enveloped viruses assemble and bud from the host cell plasma membranes (PM), including paramyxoviruses. Nipah virus (NiV) is a deadly zoonotic paramyxovirus causing yearly outbreaks in Southeast Asia with >75% mortality. NiV encodes matrix proteins (M) that drive assembly and budding. NiV-M forms dimers and interacts with membrane lipids in the host cells PM for budding. Using single-molecule localization microscopy and single-particle tracking, we show that the host F-actin maintains the nanoscale organization of NiV assembly sites at the PM. This F-actin-dependent integrity of NiV assembly sites is observed at the membrane retention stage after the assembly process is complete, rather than during the recruitment of NiV-M molecules to these sites. NiV-M interacts with actin via its C-terminal domain. We also show that the actin-branching factor, Arp2/3 complex, promotes virus-like-particle production. Meanwhile, inhibiting Arp2/3 disfavors the PM retention of NiV assembly sites and NiV-M-mediated generation of membrane protrusions, but does not affect the assembly rate. This suggests that Arp2/3-nucleated actin polymerization and branching are critical for maintaining NiV-M assembly sites at the PM, allowing it to facilitate membrane protrusion generation for virus budding. Our findings support the following model: NiV-M interacts with F-actin through its C-terminus to remain at the host PM after assembly completion. This F-actin-dependent retention is promoted by the Arp2/3-driven actin branching and polymerization, which also drives the formation of NiV-M-induced membrane protrusions necessary for virus budding. SignificanceNipah virus (NiV) is a deadly paramyxovirus capable of animal-animal and animal-human transmissions. To produce a NiV particle, the NiV matrix protein (M) must create an assembly site by binding to the surface of an infected cell and pushing the cell membrane outward for virus budding. To do so, the NiV matrix protein must co-opt or overcome an actin network underneath the cell membrane. We provide single-molecule evidence that M interacts with the actin cytoskeleton for membrane retention but not recruitment of M to existing assembly sites. This process is promoted by the Arp2/3-driven actin branching and polymerization. Our findings suggest the role of actin remodeling in NiV budding and identify a druggable site at the C-terminus of NiV-M.

microbiology↗

bioRxiv2025

Gut microbiota phospholipids regulate intestinal gene expression and can counteract the effects of antibiotic treatment

The gut microbiome influences immune and metabolic homeostasis. Our research using non-obese diabetic (NOD) mice revealed that early-life antibiotic exposure remodels the gut microbiome affecting metabolism and accelerating type 1 diabetes (T1D) incidence, with cecal material transplant (CMT) mitigating the damage. Now examining murine intestinal lipidomic profiles, we identified 747 compounds. Comparing the lipidomic profiles of cecal contents of conventional and germ-free mice and their diets, we identified 87 microbially-produced lipids reduced by antibiotic exposure but CMT-restored. Parallel analysis of human fecal lipid profiles after azithromycin-exposure showed significant alterations with substantial overlap with mice. In vitro co-culture with mouse macrophages or small intestinal epithelial cells and human colonic epithelial cells identified phospholipids that repress inflammation through the NF{kappa}B pathway. Oral administration of these phospholipids to antibiotic-treated NOD mice reduced expression of ileal genes involved in early stages of T1D pathogenesis. These findings indicate potential therapeutic anti-inflammatory roles of microbially-produced lipids.

microbiology↗

bioRxiv2025

mzLearn, a data-driven LC/MS signal detection algorithm, enables pre-trained generative models for untargeted metabolomics

Metabolite alterations are linked to diseases, yet large-scale untargeted metabolomics remains constrained by challenges in signal detection and integration of diverse datasets for developing pre-trained generative models. Here, we introduce mzLearn, a data-driven MS1 signal-detection and alignment method that runs from mzML files without user-set parameters. Across 15 public datasets, mzLearn detects 11,442 signals on average vs 7,100 (XCMS) and 4,655 (ASARI), with higher TP (89.0% vs 77.4% vs 49.6%) and lower FP (12.5% vs 17.3% vs 18.8%), while correcting instrument drifts across large cohorts without experimental QC samples. mzLearn detected 2,736 robust metabolite signals from 22 public studies (20,548 blood samples), enabling the development of pre-trained variational autoencoder for untargeted metabolomics. Learned metabolite representations reflected demographic data and when fine-tuned on unseen renal cell carcinoma data, improved risk stratification and overall survival predictions, while feature-importance analysis (SHAP) highlighted biologically plausible lipid and carnitine signals. By producing a consistent, high-quality MS1 feature matrix at scale, mzLearn paves the way for developing pre-trained foundation models for untargeted metabolomics.

bioinformatics↗

bioRxiv2025

Avoidance of fratricide and improved efficacy of CD33-MSLN CAR-iNK cells in treating acute myeloid leukemia

Acute myeloid leukemia (AML) patients are often older, which brings challenges of endurance and persistent efficacy of autologous CAR-T cell therapies. Allogenic CAR-NK cell therapies may offer reduced toxicities and enhanced anti-leukemic potential against AML. In this study, we designed a novel CD33-mesothelin loop CAR (Loop CAR) and evaluated its anti-tumor efficacy in human umbilical cord blood-derived NK (UCB-NK) cells and human pluripotent stem cell-derived NK (hPSC-iNK) cells. The Loop CAR exhibited superior cytotoxicity against dual-antigen-positive tumor cell lines and primary AML cells. To further avoid fratricide caused by endogenous CD33 expression in NK cells, we established a hPSC-derived cell line via knockout of CD33 gene (CD33KO) and engineered Loop CAR. Rather than enforced expression of exogenous CD16, we generated abundant mature CD33KO-Loop CAR-iNK cells highly expressing endogenous CD16 via an organoid induction approach. This innovative strategy effectively mitigated NK cell fratricide and significantly enhanced CD33 and mesothelin-mediated specific cytotoxicity. Moreover, the CD33KO-Loop CAR-iNK cells demonstrated superior tumor-killing activity in AML xenograft mice and significantly prolonged survival. hPSC-derived CD33KO-Loop CAR-iNK cells possess unique advantages and translational potential for treating AML.

cancer biology↗

bioRxiv2025

Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies

BackgroundT cell malignancies are highly aggressive hematological tumors with limited effective treatment options. CAR-NK cell therapy targeting CD7 has emerged as a promising approach for treating T-cell malignancies. However, conventional CAR-NK cell therapy faces the challenges of cell fratricide due to CD7 expression on both malignant cells and normal NK cells. Additionally, engineering CARs into human tissue-derived NK cells demonstrates heterogeneity, low transduction efficiency, and high manufacturing costs. MethodsThe human pluripotent stem cells (hPSCs) were genetically modified by knocking out the CD7 gene and introducing the CD7 CAR expression cassette to generate CD7 KO-CD7 CAR-hPSCs. These modified hPSCs were subsequently differentiated into CD7 KO-CD7 CAR-iNK cells using an efficient organoid induction method. The cytotoxicity of CD7 KO-CD7 CAR-iNK cells against CD7+ tumor cells was evaluated. Furthermore, we overexpressed the CXCR4 gene in CD7 KO-CD7 CAR-hPSCs and derived CXCR4-expressing CD7 KO-CD7 CAR-iNK (CRO-CD7 CAR-iNK) cells. The dynamics of CRO-CD7 CAR-iNK cells in vivo were tracked, and their therapeutic efficacy was assessed using human T-cell acute lymphoblastic leukemia (T-ALL) xenograft models. ResultsThe CD7 KO-CD7 CAR-iNK cells derived from CD7 KO-CD7 CAR-hPSCs effectively avoided fratricide, demonstrated normal expansion, and exhibited potent and specific anti-tumor activity against CD7+ T-cell tumor cell lines and primary T-ALL cells. CXCR4 overexpression in CRO-CD7 CAR-iNK cells improved their homing capacity and extended their persistence in vivo. The CRO-CD7 CAR iNK cells significantly suppressed tumor growth and prolonged the survival of T-ALL tumor-bearing mice. ConclusionsOur study provides a reliable strategy for the large-scale generation of fratricide-resistant CD7 CAR-iNK cells with robust anti-tumor effects from hPSCs, offering a promising cell product to treat T-cell malignancy.

cancer biology↗

bioRxiv2025

ST-FFPE-mIF: Integrating Spatial Transcriptomics and Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tissues Using Stereo-seq

Stereo-seq is the state-of-the-art technique, which allows capturing of spatial transcriptomic data at sub-cellular resolution and in large scale of view. Stereo-seq FFPE technique is recently launched with the capability to obtain spatially resolved gene expression in FFPE tissue sections. However, the omic information is limited to transcriptome. To delineate spatial molecular hierarchy from transcriptome to phenome, we present the protocol that implements nine-plex immunofluorescence staining with detection of spatial transcriptomics in one FFPE tissue section (short for ST-FFPE-mIF). This protocol details the modified biochemistry procedure and also provides analytical framework to achieve single-cell resolution through nuclear or membrane staining-based cell segmentation. We demonstrated the application of ST-FFPE-mIF in colorectal cancer sample to illustrate how ST-FFPE-mIF facilitates a robust analysis of spatially resolved multi-omic data at the single-cell level.

biochemistry↗

bioRxiv2025

Tet3 Mediates O-GlcNAcylation-Induced Remyelination

The failure of oligodendrocyte precursor cells (OPCs) to generate mature oligodendrocytes represents a major hurdle impeding myelin repair. However, the cellular determinants for OPC differentiation and the pharmacological targets driving remyelination remain rudimentary. Here, we demonstrate that O-GlcNAcylation intrinsically drives remyelination, in which Tet3 is one downstream effector. Enhanced O-GlcNAcylation significantly promotes OPC differentiation, whereas conditional depletion of Ogt in OPCs seriously impairs myelin formation in the developing central nervous system (CNS). Intriguingly, O-GlcNAcylation in OPCs positively correlates with the myelin status, and enhanced O-GlcNAcylation dramatically accelerates remyelination. Proteomic analyses reveal a cohort of proteins uniquely O-GlcNAcylated in OPCs. Among these, Tet3 is exclusively O-GlcNAcylated in OPCs within CNS, which in turn modulates its demethylation activity, thereby regulating myelin gene expression and remyelination. Our findings highlight the crucial role of the Ogt-Tet3 axis in OPC differentiation and suggest O-GlcNAcylation as a druggable target for treating demyelinating diseases.

developmental biology↗

bioRxiv2025

High-speed mapping of whole-mouse peripheral nerves at subcellular resolution

In contrast to the rapid advancements in mesoscale connectomic mapping of the mammalian brain, similar mapping the peripheral nervous system has remained challenging due to the bodys size and complexity. Here, we present a high-speed blockface volumetric imaging system with an optimized workflow of whole-body clearing, capable of imaging the entire adult mouse at micrometer resolution within 40 hours. Three-dimensional reconstruction of individual spinal fibers in Thy1-EGFP mice reveals distinct morphological features of sensory and motor projections along the ventral and dorsal rami. Immunostaining facilitates body-wide mapping of sympathetic nerves and their branches, highlighting their perivascular patterns in limb muscles, bones, and most visceral organs. Viral tracing elucidates the fine architecture of vagus nerves and individual vagal fibers, revealing unexpected projection routes to various organs. Our approach offers an effective means to achieve a holistic understanding of cellular-level interactions among different systems that underlie body physiology and disease. HighlightsO_LIImaging of whole adult mouse at uniform subcellular resolution within 40 hours C_LIO_LIReconstruction of 191 thoracic spinal neuron projections for Thy1-EGFP mice C_LIO_LIMapping of immunolabeled sympathetic projections and their perivascular patterns C_LIO_LIResolving virus-labeled architecture of vagus nerves and complex single-fiber routes C_LI

neuroscience↗

bioRxiv2025

Super-omics and PCAS reveal rheumatoid arthritis as a tumor-like disease

Rheumatoid arthritis (RA) is a debilitating systemic autoimmune disorder that significantly impairs quality of life. To elucidate the molecular alterations in RA progression, we performed comprehensive super-omics analyses on synovial tissues from patients with joint trauma, arthritis, and RA. These analyses included transcriptomics, proteomics, metabolomics, microbiomics, and fourteen PTMs (phosphorylation, acetylation, lactylation, O-GlcNAc glycosylation, arginine monomethylation, lysine monomethylation, lysine dimethylation, lysine trimethylation, succinylation, malonylation, glutarylation, tyrosine nitration, N-glycosylation, and O-glycosylation). Additionally, we developed a protein-centered association study (PCAS) method to integrate these complex datasets. Using this approach, we identified key proteins, such as STK17B, and its interactors, which may be crucial in RA pathogenesis. Tumor-like features, including aberrant angiogenesis and epithelial-mesenchymal transition, were observed in RA, alongside the potential involvement of oncogenes and tumor suppressor genes. Finally, we constructed a molecular interaction blueprint of RA, providing a comprehensive framework for advancing RA pathogenesis, diagnosis, and therapy.

immunology↗

bioRxiv2025

Persistent interferon signaling that causes sensory neuron plasticity and pain in arthritis

While the inflammatory processes in rheumatoid arthritis have been described, mechanisms driving pain are poorly defined. Here, we used a multitude of approaches to uncover the neural basis, mediators, intracellular signaling pathway and the mechanism of inflammatory pain. In cartilage autoantibody-induced arthritis mice, an early immune-activation and a cytokine storm were mainly driven by vascular cells and monocyte/macrophages in the dorsal root ganglion. However, persistently elevated interferons and receptor-activation of the MNK1/2-eIF4E signaling pathway at all disease phases caused sensory-motor dysfunction and pain by inducing hyperexcitability and sensitization of Gfra3+ sensory neurons. Like mice, human sensory neurons expressed interferon receptors and interferons were elevated only in individuals with painful rheumatoid arthritis. Signaling pathway inhibition in vivo reversed pain and restored limb function. The finding that joint pain before and during arthritis is caused by a defined cytokine and signaling pathway holds promise for targeted therapies for pain relief in arthritis.

neuroscience↗

bioRxiv2025

Pluripotent stem cell-derived NK progenitor cell therapy prevents tumour occurrence and eradicates minimal residual disease

The lack of persistence and short-term efficacy presents a major challenge for CAR-NK cell therapy. Here, we addressed this issue by developing pluripotent stem cell-derived NK lineage-committed progenitor (iNKP) cell therapy. For the first time, we generated abundant iNKP cells via an organoid culture system. The iNKP cells, engineered to express CXCR4 and chimeric antigen receptors (CAR), efficiently migrated to the bone marrow and generated CAR-iNK cells persisting in peripheral blood (PB) for over 80 days. Notably, CAR-iNKP cell therapy durably protected animals from tumour occurrence. Furthermore, a single low-dose infusion of CAR-iNKP cells following conventional chemotherapy eradicated minimal residual disease (MRD), leading to long-term complete remission. Our findings present a novel strategy to overcome the limitations of traditional CAR-NK cell therapy and offer dural breakthroughs for the prevention of tumour occurrence and relapse.

cancer biology↗

bioRxiv2025

Biochemical Profiling and Structural Basis of ADAR1-Mediated RNA Editing

ADAR1 is a pivotal regulator in RNA-induced immune responses by catalyzing the conversion of adenosine to inosine on double-stranded RNA. Mutations on ADAR1 are associated with human autoimmune disease, and targeting ADAR1 has been proposed for cancer immunotherapy. However, the molecular mechanisms governing ADAR1-mediated RNA editing remain enigmatic. Here, we provide detailed biochemical and structural characterizations of human ADAR1. Our biochemical profiling reveals that ADAR1 editing is both sequence and RNA duplex length-dependent, but can well tolerate mismatches near the editing site. Moreover, our high-resolution structures of ADAR1-RNA complexes, coupled with mutagenesis studies, revealed the molecular basis for RNA binding, substrate selection, dimerization, and the crucial role of the RNA-binding domain 3 for ADAR1 editing. The ADAR1 structures also help explain the potential defects of disease-associated mutations, where biochemical and RNA-sequencing analysis further indicate some of the mutations preferentially impact the editing of RNAs with short duplex. Our findings illustrate the molecular mechanism of ADAR1 editing and provide clues for deciphering its role in immune regulation and drug targeting. HIGHLIGHTSO_LIBiochemical profiling of ADAR1 RNA substrate preference C_LIO_LIAtomic resolution structures of ADAR1 with two physiological RNA substrates C_LIO_LIDisease-related mutations of ADAR1 preferentially impact RNA editing with short dsRNA. C_LIO_LIRNA-binding domain 3 is essential for ADAR1 RNA capture and editing C_LI

biochemistry↗

bioRxiv2024

A poly(A) polymerase and oligo(dT)-dependent method for the purification of engineering circular RNAs that enhances protein expression in eukaryotic cells

Circular RNA (circRNA) has garnered significant attention as a promising therapeutic tool due to its remarkable stability and resistance to exonuclease degradation. However, the development of scalable and efficient purification methods remains a critical challenge. In this study, we propose and evaluate a novel purification strategy for engineered circular RNA (PAPdt), which leverages poly(A) polymerase and oligo(dT) affinity chromatography. Using poly(A) polymerase, we add poly(A) tails of over 200 nucleotides to the 3-OH ends of all linear RNA impurities in a circular RNA preparation. These linear RNAs are then separated from the circular RNA via oligo(dT) affinity chromatography. The linear impurities, bearing longer poly(A) tails, exhibit extended retention on the oligo(dT) column, whereas the circular RNA, with a shorter poly(A) sequence, elutes more quickly. By stepwise elution with ultrapure water, we effectively separate the circular RNA from the linear contaminants. This method offers a fundamental solution to the purification of circular RNA, combining high efficiency, purity, and cost-effectiveness.

bioengineering↗