Biology subjects

Yang, Y.

Publications and source records attributed to Yang, Y..

At least 559 records · Page 31Linked to original sources

bioRxiv2024

Bibacillin 1: A two-component lantibiotic from Bacillus thuringiensis

Here we describe bibacillin 1 - a two-component lantibiotic from Bacillus thuringiensis. The peptides that comprise bibacillin 1 are modified by a class II lanthipeptide synthetase Bib1M producing two peptides with non-overlapping ring patterns that are reminiscent of cerecidin and the short component of the enterococcal cytolysin (CylLS"), a virulence factor associated with human disease. Stereochemical analysis demonstrated that each component contains LL-methyllanthionine and DL-lanthionine. The mature bibacillin 1 peptides showed cooperative bactericidal activity against Gram-positive bacteria, including members of ESKAPE pathogens, and weak hemolytic activity. Optimal ratio studies suggest that bibacillin 1 works best when the components are present in a 1:1 ratio, but near optimal activity was observed at ratios strongly favouring one component over the other, suggesting that the two peptides may have different but complementary targets. Mechanism of action studies suggest a lipid II-independent killing action distinguishing bibacillin 1 from two other two-component lantibiotics haloduracin and lacticin 3147. One of the two components of bibacillin 1 showed cross reactivity with the cytolysin regulatory system. These result support the involvement of bibacillin 1 in quorum sensing and raise questions about the impact of CylLS"-like natural products on lanthipeptide expression in diverse bacterial communities.

biochemistry↗

bioRxiv2024

Exploring Transcriptional Regulation of Soybean Tissue Development with Machine Learning Method

Soybean is one of the most important crops that is widely demanded by people in daily lives. Measuring the transcriptome of a tissue or condition is a powerful way to detect changes in genetic adaptation. However, it remains difficult to identify the key genes in transcriptional regulation most likely to explain specific traits. Here, we outline a machine learning method that utilizes publicly available soybean RNA-seq data by uncovering conserved expression patterns of genes controlled by transcription factor (TF) / transcription regulator (TR) genes in soybean tissues across time and space under various conditions. In addition to its function in gene expression homeostasis, we can also identify important TF/TR genes related to soybean leaf, stem and root tissue development. Combining with co-expression modules highly expression in the tissue, we also highlight the impact of candidate TF/TR genes in the module in different tissues that may shape the dynamics of soybean development. Together, our results revealed the importance of transcriptional regulatory module analysis in unraveling key traits in the soybean development, in particular those TFs/TRs and their target genes.

bioinformatics↗

bioRxiv2024

A Self-Assembling Immune-Featured Osteosarcoma Patient/PDX Derived Organoid Model and Biobank for Personalized Immune Therapy

Osteosarcoma (OS) exhibit intra- and inter-heterogeneity, complicating the exploration of effective therapeutic strategies. Traditional in vitro and in vivo models are limited in inheriting biological and genomic heterogeneities of OS patients, even in inheriting the features on tumor microenvironment. The prolonged generation time of current models makes the drug development of OS slow and is not suitable to clinically rapid timing. Here, we introduce methods for generating and biobanking patient/PDX-derived osteosarcoma organoids (OS PD(X)Os) that recapitulate the histological, biological and genomic features of their paired OS patients. OS PD(X)Os can be generated quickly with high reliability in vitro or transplanted to immunodeficient mice. We further demonstrate an immune-featured OS PD(X)O (named iOS) model and its method for testing personalized chemotherapy response, personalized immune therapeutic strategy and target drug development, such as a novel PRMT5MTA inhibitor ARPN2169 on MTAP-deleted OS. Our studies show that iOS models maintain many typical features of OS and could be rapidly employed to investigate patient-specific therapeutic strategies. Additionally, our biobank establishes a rich resource for basic, translational and even clinical OS researches.

cancer biology↗

bioRxiv2024

Celastrol binds to pyruvate kinase and imitates the metabolic reprogramming of ATP

ATP is the final product of glycolysis and the TCA cycle. However, the counter-regulation of glycosis and TCA by ATP is poorly understood. Here we show that ATP analog celastrol (CLT) binds to the ATP binding pocket on pyruvate kinase PKM (PKM) while inducing allosteric regulation of PKM. Quantum calculation predicts hydrogen bond formation between CLT and asparagine. Liquid chromatography-mass spectrometry further identifies PKM as CLTs target. The inhibition of PKM is stronger and longer for CLT while weak and short for ATP. Notably, CLT-PKM interaction perfectly underlies the hypoglycemic effects by forming glucose carbon flux U turn before PKM. Besides, the PKM allostery induces a tricarboxylic acid (TCA) vortex which could promote amino acid and lipid degradation as the energy compensation, leading to a significant weight loss. Additionally, CLT exerts efficient antioxidant effects by altering the glucose flux to strengthen the pentose phosphate pathway. Consequently, the CLT-PKM interaction vividly reproduces the ATP-PKM interaction named "ATP resistance" in the diabetes pathogenesis.

pharmacology and toxicology↗

bioRxiv2024

Extraction-free colorimetric RT-LAMP for SARS-CoV-2 RNA detection from saliva

AimTo develop a rapid and easy diagnostic assay for detection of SARS-CoV-2 RNA presented in saliva samples. MethodThe color-based RT-LAMP was used to detect nucleocapsid (N) gene of SARS-CoV-2 without RNA extraction from saliva. ResultsRNA spiked saliva can be used directly for cDNA synthesis after heat inactivation of the saliva and diluted 2-fold with either water or PBS. For both PCR and LAMP, 20% of saliva did not have obvious effect on the reaction. Saliva did not interfere with RT-LAMP when the volume of saliva was less than 20% of the total volume. The sensitivity of the RT-LAMP reached to 1.034x10-5 ng/{micro}l (475 copies/l). The RT-LAMP assay was validated by testing 20 RNA spiked saliva samples. The assay specificity was similar to that of data without saliva. ConclusionsThe RT-LAMP colorimetric assay can be used as a screening method with the advantages of being rapid, easy to use than the qRT-PCR.

microbiology↗

bioRxiv2024

Therapeutic potential of red blood cell-derived extracellular vesicles in reducing neuroinflammation and protecting against retinal degeneration.

Neuroinflammation is a pathological process mediated through immune cell activation and pro-inflammatory cytokine release, resulting in neuronal cell death. In the central nervous system (CNS), neuroinflammation is a characteristic feature underlying the onset and progression of retinal and neurodegenerative diseases. Targeting neuroinflammation to reduce neuronal cell death and protect against visual and cognitive declines is therefore a key therapeutic strategy. However, due to the complex and multi-faceted nature of these diseases, to date there has been little therapeutic success with single target approaches insufficient to tackle widespread and multi-pathway inflammatory cascades. Furthermore, as the retina and brain reside within immune-privileged environments, a major challenge in treating these diseases is producing and delivering a therapeutic that, in itself, does not exacerbate inflammation. Extracellular vesicles (EV), derived from red blood cells (RBC EV), present a promising solution to overcome these hurdles, due to their innate ability to cross blood-tissue barriers, biocompatible nature, and their broad anti-inflammatory properties to modulate complex neuroinflammatory pathways. This study therefore investigated the therapeutic potential of RBC EV in mediating neuroinflammation using an in-vivo photo-oxidative damage model of retinal degeneration as a model for CNS neuroinflammation. In this work, we developed a novel incubation pipeline using N1 medium supplement and superoxide dismutase (SOD) supplementation to promote the production of safe, neuroprotective, and anti-inflammatory RBC EV. Delivery of RBC EV in vivo, was shown to be safe with strong penetration across all retinal layers. Further, therapeutic administration of RBC EV via local intravitreal injection significantly reduced inflammation and cell death and preserved retinal function. Notably, strong safety and therapeutic efficacy was also demonstrated in the retina following systemic (intraperitoneal) administration, highlighting a potential game-changing approach for less-invasive therapeutic delivery to the CNS. Finally, multi-omic analyses and in vitro findings supported an anti-inflammatory mechanism-of-action, with RBC EV modulating pro-inflammatory cytokine release, including those known to be involved in the pathogenesis of retinal and neurodegenerative diseases. Taken together, these findings highlight the broad applicability of RBC EV in treating neuroinflammation in the CNS, presenting a scalable and effective treatment approach for these currently untreatable diseases.

neuroscience↗

bioRxiv2024

Evolution and Diversification of the Aposematic Poison Frog, Oophaga pumilio, in Bocas del Toro

The aposematic strawberry poison frog, Oophaga pumilio, is an iconic model system for studying the evolution and maintenance of color variation. Through most of its range, this frog is red with blue limbs. However, frogs from the Bocas del Toro Province, Panama, show striking variance in color and pattern, both sympatrically and allopatrically. This observation contradicts standard models of the evolution of aposematism and has led to substantial speculation about its evolutionary and molecular causes. Since the enigma of O. pumilio phenotypic variation is partly unresolved because of its large, [~] 6.7 Gb genome, we here sequence exomes from 347 individuals from ten populations and map a number of genetic factors responsible for the color and pattern variation. The kit gene is the primary candidate underlying the blue-red polymorphism in Dolphin Bay, where an increase in melanosomes is correlated with blue coloration. Additionally, the ttc39b gene, a known enhancer of yellow-to-red carotenoid conversion in birds, is the primary factor behind the yellow-red polymorphism in the Bastimentos West area. The causal genetic regions show evidence of selective sweeps acting locally to spread the rare phenotype. Our analyses suggest an evolutionary model in which selection is driving the formation of new morphs in a dynamic system resulting from a trade-off between predation avoidance, intraspecific competition, and mate choice.

evolutionary biology↗

bioRxiv2024

SGLT2 inhibitors activate pantothenate kinase in the human heart

Inhibitors of sodium glucose cotransporter-2 (SGLT2i) demonstrate strong symptomatic and mortality benefits in the treatment of heart failure but appear to do so independently of SGLT2. The relevant pharmacologic target of SGLT2i remains unclear. We show here that SGLT2i directly activate pantothenate kinase 1 (PANK1), the rate-limiting enzyme that initiates the conversion of pantothenate (vitamin B5) to coenzyme-A (CoA), an obligate co-factor for all major pathways of fuel use in the heart. Using stable-isotope infusion studies, we show that SGLT2i promote pantothenate consumption, activate CoA synthesis, rescue decreased levels of CoA in human failing hearts, and broadly stimulate fuel use in ex vivo perfused human cardiac blocks from patients with heart failure. Furthermore, we show that SGLT2i bind to PANK1 directly at physiological concentrations and promote PANK1 enzymatic activity in assays with purified components. Novel in silico dynamic modeling identified the site of SGLT2i binding on PANK1 and indicated a mechanism of activation involving prevention of allosteric inhibition of PANK1 by acyl-CoA species. Finally, we show that inhibition of PANK1 prevents SGLT2i-mediated increased contractility of isolated adult human cardiomyocytes. In summary, we demonstrate robust and specific off-target activation of PANK1 by SGLT2i, promoting CoA synthesis and efficient fuel use in human hearts, providing a likely explanation for the remarkable clinical benefits of SGLT2i.

biochemistry↗

bioRxiv2024

A new regulator of sporulation sheds light on spore morphogenesis and ballistospory in mushroom-forming fungi

Sporulation is the most widespread means of reproduction and dispersal in fungi. In the Basidiomycota, sexual spores are produced on specialised cells known as basidia, from which they are discharged forcibly by a powered process called ballistospory, the highest known acceleration in nature. However, the genetics of sporulation, in particular postmeiotic events related to spore morphogenesis and ballistospory, remain poorly known. Here, we explore the genetics of these processes, based on a new, highly conserved transcription factor, Sporulation-Related Regulator 1 (SRR1), and its putative downstream regulatory network. Reverse genetics of Srr1 in the model mushroom Coprinopsis cinerea and commercially produced oyster mushroom indicated a conserved role of Srr1 in sporulation across Agaricomycetes. RNA-Seq analysis and motif-based inference of a hypothetical SRR1 gene regulatory network allowed delimiting putative targets regulated by SRR1 in a direct and indirect manner. Using this network and comparative genomics, we identified genes associated with ballistospory, including a putative SRR1-target chitinase, which was found to be required for normal spore production and morphology. Overall, our study offers new insights into the genetic mechanisms governing postmeiotic spore morphogenesis and ballistospory in the Agaricomycetes.

microbiology↗

bioRxiv2024

Modulation Of SUDEP By Central Serotonergic Cooperating with Noradrenergic Circuits: A Synergistic-Dependent Manner

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Despite previous accumulating evidence has shown that seizure-induced respiratory arrest (S-IRA) may play the main contributor to SUDEP as an initiating event preeminent cause of mortality, the specific underlying mechanism of action remains unclear. Based on our previous work, serotonin (5-HT) signaling in the dorsal raphe nucleus (DRN) is strongly implicated in S-IRA in animal models, including the DBA/1 mice, on the meanwhile, norepinephrine (NE) neurons of the locus coeruleus (LC) also plays a vital role in regulating respiratory function on its own. Superficially, monoaminergic neuron, as important neurotransmitters in the central nervous system, have similar modes of action in the maintenance of nervous system balance, and each of them has a regulatory effect on SUDEP. However, it remains to be investigated whether monoaminergic neuron family (NE and 5-HT) are related in the mechanism of regulating SUDEP, what is even more curious is whether the two are intrinsically linked. Thus, we hypothesize neural mechanism of central noradrenergic and serotonergic circuits in modulating SUDEP in a synergistic-dependent manner, this endeavor will culminate in a significant breakthrough in elucidating the precise mechanism of action underlying SUDEP. In our study, we will use chemogenetics, optogenetics, calcium signal recording, and bidirectional tracing to explore the internal mechanism of DR-LC regulating the occurrence of SUDEP, and by specifically injecting 5-HT2AR antagonist Ketanserin (KET) and/or NE-1R antagonist Prazosin into the pre-Botzinger complex (PBC), it was finally elucidate that the DR-LC-PBC network can effectively reduce the incidence of SIRA. We firstly proposed a powerful target for exploring the reduction of the incidence of SUDEP, which has great clinical translation potential.

neuroscience↗

bioRxiv2024

A Molecular Image-based Explainable Artificial intelligence Framework Identifies Novel Candidate Antibiotics

The continued growth of antibiotic resistance and the slowing of antibiotic discovery poses a large challenge in fighting infectious diseases. Recent advances in Artificial intelligence (AI) technologies offer a time- and cost-effective solution for the rapid development of effective antibiotics. In this study, we presented an explainable AI framework from a pre-trained model using 10 million drug-like molecular images. Specifically, we created a fine-tuned ImageMol from experimental Staphylococcus aureus inhibition assays which contained 24,521 molecules consisting of 516 active compounds and 24,005 non-active compounds. Our optimized AI model achieved a strong AUROC of 0.926. The model was then used to predict the antibiotic activities from 10,247 FDA-approved, clinically investigational, or experimental molecules from the DrugBank database. After further filtering, 340 molecules were identified to have antibacterial behavior while simultaneously being dissimilar to known antibiotics. Finally, 76 candidates were identified as FDA-approved drugs for other applications. Thus, those candidates can be repurposed into needed novel antibiotics. We further illustrated explainable molecular images for top predicted candidate drugs via Gradient-weighted Class Activation Mapping (Grad-CAM) heatmap analysis. In summary, the presented molecular image-based AI model in drug discovery could be highly favorable due to its high performance, speed, and biological interpretation.

pharmacology and toxicology↗

bioRxiv2024

scEccDNAdb: an integrated single-cell eccDNA resource for human and mouse

Extrachromosomal circular DNA (eccDNA), an extrachromosomal circular structured DNA, is extensively found in eukaryotes. Exploring eccDNA at the single-cell level contributes to understanding heterogeneity, evolution, development, and specific functions within cells. Nevertheless, the high-throughput identification methods for single-cell eccDNA are complex, and currently mature and widely applicable technologies are lacking. Those factors have led to a scarcity of resources for studying eccDNA at the single-cell level. Therefore, using available single-cell whole-genome sequencing (WGS) data, we have constructed a comprehensive eccDNA database named scEccDNAdb (https://lcbb.swjtu.edu.cn/scEccDNAdb/). Presently, scEccDNAdb comprises 3,195,464 single-cell eccDNA entries from both disease/health human and mouse samples, which provides comprehensive annotations including oncogenes, typical enhancers, super-enhancers, CTCF binding sites, SNPs, chromatin accessibility, eQTLs, transcription factor binding sites, motifs, and SVs. Additionally, it provides nine online analysis and visualization tools, facilitating the generation of publication-quality figures for eccDNA analysis through the upload of customized files. Overall, scEccDNAdb represents the first comprehensive database known to us for exploring and analyzing single-cell eccDNA data in diverse cell types, tissues, and species. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/604058v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@bd23f8org.highwire.dtl.DTLVardef@1847c7eorg.highwire.dtl.DTLVardef@109717forg.highwire.dtl.DTLVardef@fa56b7_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

FLASH radiotherapy using high-energy X-rays: validation of the FLASH effect triggered by a compact single high-energy X-ray source device

PurposeThis preclinical study aimed to verify the FLASH effect of compact single high-energy X-ray source (CHEXs) and to explore whether three irradiations with single-gantry rotation two 30 s pauses can generate FLASH effect in mice. Materials and methodsThe absolute dose and pulsed beam of the CHEXs were measured using an EBTXD radiochromic film and fast current transformer. Healthy C57BL/6J female mice and a subcutaneous tumor model were irradiated under different conditions: sham (control), FLASH-RT (FLASH1: delivering the total dose in 1 fraction; FLASH3: delivering the total dose with two 30 second pauses to simulate a three-field delivery where the gantry rotation is occurring within 30 seconds), and conventional dose rate radiotherapy (CONV-RT). Various total doses were administered to the corresponding normal tissues (whole thorax, 30 Gy; whole abdomen, 12 Gy; and skin, 36 Gy) and tumors (CT26, 16.5 Gy; and LLC, 18 Gy). Survival status, normal tissue damage, and tumor growth suppression were recorded in each group. ResultsThe average dose rate of the CHEXs exceeded 40 Gy/s. For whole-thorax and skin irradiation, both FLASH1 and FLASH3 demonstrated protective effects. For whole-abdomen irradiation, FLASH1 exhibited a superior protective effect. No significant differences in tumor growth responses were observed between the FLASH1, FLASH3, and CONV-RT groups (P>0.05). ConclusionThis study confirmed that the FLASH effect could be triggered using CHEXs FLASH radiotherapy, and demonstrated that three irradiations with single gantry rotation two 30 s pauses can trigger the FLASH effect, indicating the potential benefit of CHEXs 3D conformal radiotherapy. Our findings indicate that further clinical trials on CHEXs are warranted.

cancer biology↗

bioRxiv2024

OPUS-BFactor: Predicting protein B-factor with sequence and structure information

Protein B-factor, also known as the Debye-Waller factor, measures the fluctuation of an atom around its average position. It serves as a crucial indicator of protein flexibility and dynamics. However, accurately predicting the B-factor of C atoms remains challenging. In this work, we introduce OPUS-BFactor, a tool for predicting the normalized protein B-factor. OPUS-BFactor operates in two modes: the first mode, OPUS-BFactor-seq, uses sequence information as input, allowing predictions based solely on protein sequence; the second mode, OPUS-BFactor-struct, uses structural information, requiring the 3D structure of the target protein. Evaluation on three test sets, including recently released targets from CAMEO and CASP15, demonstrates that OPUS-BFactor significantly outperforms other B-factor prediction methods. Therefore, OPUS-BFactor is a valuable tool for predicting protein properties related to the B-factor, such as flexibility, thermal stability, and region activity.

bioinformatics↗

bioRxiv2024

Clathrin-associated carriers enable recycling through a kiss-and-run mechanism

Endocytosis and recycling control the uptake and retrieval of various materials, including membrane proteins and lipids, in all eukaryotic cells. These processes are crucial for cell growth, organization, function, and environmental communication. However, the mechanisms underlying efficient, fast endocytic recycling remain poorly understood. Here, by utilizing a biosensor and imaged-based screening, we uncover a novel recycling mechanism that couples endocytosis and fast recycling, which we name the clathrin-associated fast endosomal recycling pathway (CARP). Clathrin-associated tubulovesicular carriers containing clathrin, AP1, Arf1, Rab1, and Rab11, while lacking the multimeric retrieval complexes, are generated at subdomains of early endosomes, and then transported along actin to cell surfaces. Unexpectedly, the clathrin-associated recycling carriers undergo partial fusion with the plasma membrane. Subsequently, they are released from the membrane by dynamin and reenter cells. Multiple receptors utilize and modulate CARP for fast recycling following endocytosis. Thus, CARP represents a novel endocytic recycling mechanism with kiss-and-run membrane fusion.

cell biology↗

bioRxiv2024

Alzheimer Disease Knowledge Graph Enhances Knowledge Discovery and Disease Prediction

BackgroundAlzheimers disease (AD), a progressive neurodegenerative disorder, continues to increase in prevalence without any effective treatments to date. In this context, knowledge graphs (KGs) have emerged as a pivotal tool in biomedical research, offering new perspectives on drug repurposing and biomarker discovery by analyzing intricate network structures. Our study seeks to build an AD-specific knowledge graph, highlighting interactions among AD, genes, variants, chemicals, drugs, and other diseases. The goal is to shed light on existing treatments, potential targets, and diagnostic methods for AD, thereby aiding in drug repurposing and the identification of biomarkers. ResultsWe annotated 800 PubMed abstracts and leveraged GPT-4 for text augmentation to enrich our training data for named entity recognition (NER) and relation classification. A comprehensive data mining model, integrating NER and relationship classification, was trained on the annotated corpus. This model was subsequently applied to extract relation triplets from unannotated abstracts. To enhance entity linking, we utilized a suite of reference biomedical databases and refine the linking accuracy through abbreviation resolution. As a result, we successfully identified 3,199,276 entity mentions and 633,733 triplets, elucidating connections between 5,000 unique entities. These connections were pivotal in constructing a comprehensive Alzheimers Disease Knowledge Graph (ADKG). We also integrated the ADKG constructed after entity linking with other biomedical databases. The ADKG served as a training ground for Knowledge Graph Embedding models with the high-ranking predicted triplets supported by evidence, underscoring the utility of ADKG in generating testable scientific hypotheses. Further application of ADKG in predictive modeling using the UK Biobank data revealed models based on ADKG outperforming others, as evidenced by higher values in the areas under the receiver operating characteristic (ROC) curves. ConclusionThe ADKG is a valuable resource for generating hypotheses and enhancing predictive models, highlighting its potential to advance ADs disease research and treatment strategies.

bioinformatics↗

bioRxiv2024

Large-scale genome analyses provide insights into Hymenoptera evolution

The order Hymenoptera includes a large number of species with diverse lifestyles and is known for its significant contributions to natural ecosystems. To better understand the evolution of this diverse order, we performed large-scale comparative genomics on 131 species from 13 superfamilies, covering most representative groups. We used these genomes to reveal an overall pattern of genomic change in terms of gene content and evolutionary rate throughout hymenopteran history. We identified genes that possibly contributed to the evolution of several key innovations, such as parasitoidism, wasp-waist, sting, and secondary phytophagy. We also discovered the distinct genomic trajectories between the clade containing major parasitoid wasps (Parasitoida) and stinging species (Aculeata) since their divergence, which are involved in many aspects of genomic change, such as rapidly evolving gene families, gene gain and loss, and metabolic pathway evolution. In addition, we explored the genomic features accompanying the three independent evolution of secondary phytophagy. Our work provides insights for understanding genome evolution and the genomic basis of diversification in Hymenoptera.

genomics↗

bioRxiv2024

A Drug-Elicitable Alternative-Splicing Module (DreAM) for Tunable AAV Expression and Controlled Myocardial Regeneration

Adeno-associated virus (AAV) is a major vector for gene therapy. A technique to fine-tune the time and level of AAV expression is lacking, which greatly restricts indication choice, therapeutic efficacy and safety. To solve this problem, here we developed a drug-elicitable alternative-splicing module (DreAM) responsive to risdiplam, an FDA-approved alternative splicing modulator. Risdiplam activates DreAM-regulated AAV expression in a dose-dependent manner with an over 2000-fold inducible change depending on the inducer dosage and the organ of interests. With a temporally resolution of a couple of days, DreAM could repeatedly activate AAV expression, determined by the frequency and duration of risdiplam administration. As an example of DreAM-realized gene therapy, this technique was used to control AAV-based cardiac delivery of YAP5SA, a potent cardiomyocyte regeneration factor. DreAM transiently activated AAV-YAP5SA, establishing the dedifferentiation-proliferation-redifferentiation cycle in cardiomyocytes. Consequently, DreAM fulfilled the regenerative capacity of AAV-YAP5SA in myocardial infarction while circumventing toxicity associated with prolonged AAV-YAP5SA expression. Together, these data demonstrated a tremendous potential of DreAM to enhance the efficacy, safety and applicable scope of gene therapy.

bioengineering↗