INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Lele Gong,Yuanyuan Zhang,Lele Wang,Xuyang Zhao,Lucai Wang,Xiangqi Qiu,Xilong Yang,Wenhui Zhu,Lijie Lv,Yunzhe Kang,Yanan Wu,Angke Zhang,Yongkun Du,Xuannian Wang,Gaiping Zhang,Aijun Sun,Guoqing Zhuang
The African swine fever virus (ASFV) continues to pose significant economic and pandemic risks. Consequently, discovering new, efficient vaccines is crucial. Messenger RNA (mRNA) vaccines have emerged as promising candidates, providing minimal risk of insertional mutagenesis, high safety profiles, effectiveness, rapid scalability in production, and cost-effectiveness. In this study, we have developed an ASF p30 mRNA vaccine candidate (mRNA/Man-LNP) employing mannose-modified lipid nanoparticles (LNPs). The mRNA/Man-LNP exhibited effective antigen presentation and facilitated dendritic cells (DCs) maturation. Notably, it elicited strong IgG titers and activated CD4 + and CD8 + T-cells in immunized mice, all while adhering to stringent biosafety standards. This investigation demonstrates that mRNA/Man-LNP can trigger both humoral and cellular immune responses, suggesting its potential as a potent and promising vaccine candidate for controlling African swine fever (ASF).
研究领域:
兽医学
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免疫学
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分子生物学
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病毒学
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DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2025
·
IF 26.6
Xu Saijuan,Liang Dan,Wang Qiudao,Cheng Yan,Xie Da,Gui Yang,Zhang Haokun,Feng Changrui,Zhao Feiyan,Ren Wendan,Sun Gongrui,Yang Yang,Li Lin,Lai Yongrong,Fu Bin,Lu Yuming,Wang Zi Jun,Wu Yuxuan
Ex vivo autologous haematopoietic stem cell (HSC) gene therapy provides a promising treatment option for haematological disorders. However, current methods involve complex processes and chemotherapeutic conditioning, leading to limited accessibility for treatment and major side effects. Here we develop antibody-free targeted lipid nanoparticles (LNPs) for mRNA delivery to HSCs in vivo, enabling efficient base editing of the γ-globin gene ( HBG1/2 ) promoter target in human HSCs to reactivate fetal haemoglobin in derived erythroid cells. Delivery of ABE8e/sgRNA mRNA with optimized LNPs achieves efficient in vivo base editing of HBG1/2 in transfusion-dependent β-thalassaemia (TDT) patient-derived HSCs engrafted in immunodeficient NCG-X mice, showing restored globin chain balance in erythroid cells. Our research indicates that using LNPs for genome editor delivery achieves efficient editing of endogenous genes of human HSCs. This non-viral delivery system eliminates the need for collecting or mobilizing HSCs, providing a potent and one-time treatment potential for blood disorders such as sickle cell disease and TDT.
研究领域:
遗传学
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分子生物学
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生物技术
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基因治疗
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Chunwei Tang,Weiqiang Jing,Kun Han,Zhenmei Yang,Shengchang Zhang,Miaoyan Liu,Jing Zhang,Xiaotian Zhao,Ying Liu,Chongdeng Shi,Qihao Chai,Ziyang Li,Maosen Han,Yan Wang,Zhipeng Fu,Zuolin Zheng,Kun Zhao,Peng Sun,Danqing Zhu,Chen Chen,Daizhou Zhang,Dawei Li,Shilei Ni,Tao Li,Jiwei Cui,Xinyi Jiang
Sepsis, which is the most severe clinical manifestation of acute infection and has a mortality rate higher than that of cancer, represents a significant global public health burden. Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection and further host immune paralysis are the leading causes of sepsis-associated death, but limited clinical interventions that target sepsis have failed to effectively restore immune homeostasis to enable complete eradication of MRSA. To restimulate anti-MRSA innate immunity, we developed CRV peptide-modified lipid nanoparticles (CRV/LNP-RNAs) for transient in situ programming of macrophages (MΦs). The CRV/LNP-RNAs enabled the delivery of MRSA-targeted chimeric antigen receptor (CAR) mRNA (SasA-CAR mRNA) and CASP11 (a key MRSA intracellular evasion target) siRNA to MΦs in situ, yielding CAR-MΦs with boosted bactericidal potency. Specifically, our results demonstrated that the engineered MΦs could efficiently phagocytose and digest MRSA intracellularly, preventing immune evasion by the “superbug” MRSA. Our findings highlight the potential of nanoparticle-enabled in vivo generation of CAR-MΦs as a therapeutic platform for multidrug-resistant (MDR) bacterial infections and should be confirmed in clinical trials.
研究领域:
传染病学
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纳米技术
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免疫学
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药学
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产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Elham Ghashghaei,Minghui Wang,Ahmed Mijiyawa,Hai Lin
Amino acids in the brain modulate eating behavior and energy balance. The aim of the present study was to investigate the effects of DL-methionine (DL-Met), L-lysine monohydrochloride (L-Lys-HCl), and taurine (Tau) on feed intake and the mRNA expression levels of appetite-related hypothalamic neuropeptides in chicks. DL-Met, L-Lys-HCl, or Tau was intracerebroventricularly (ICV) administered to 5-day-old layer-type chicks, and the feed intake was recorded until 1 h post-injection. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of neuropeptide Y ( NPY ) and its receptors, agouti-related protein ( AgRP ), pro-opiomelanocortin ( POMC ), cocaine- and amphetamine-regulated transcript ( CART ), and melanocortin receptors. Our results indicated that injection time and treatment have a significant effect on food intake. Food intake decreased significantly at 30 and 60 minutes after ICV administration of DL-Met (1.678 μmol), L-Lys-HCl (6.856 μmol), and Tau (5.006 μmol) compared to the control group ( P > 0.05). On the contrary, a high dose of each amino acid did not alter feed intake ( P > 0.05). The result showed that ICV injection of DL-Met (1.678 μmol) significantly decreased the mRNA expressions of NPY , NPY4R , and NPY6R ( P < 0.05), but had no significant effect on the mRNA expressions of NPY1R, NPY5R, and AgRP in the hypothalamus ( P > 0.05). Similarly, ICV injection of L-Lys-HCl (6.856 μmol) and Tau (5.006 μmol) significantly decreased mRNA levels of NPY, NPY4R, and NPY6R ( P < 0.05), without affecting the mRNA expressions of NPY1R, NPY5R, and AgRP ( P > 0.05). DL-Met had no effect on anorexigenic gene expression ( P > 0.05). L-Lys-HCl upregulated MC1R ( P < 0.05), and Tau upregulated POMC and MC3R ( P < 0.05), and both had no influence on CART, MC4R , or MC5R ( P > 0.05). The result suggests that both orexigenic and anorexigenic neuropeptide genes are involved in the effects of DL-Met, L-Lys-HCl, and Tau. The effect of DL-Met, L-Lys-HCl, and Tau acts in a dose-dependent manner in the hypothalamus to influence feed intake.
研究领域:
动物科学
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神经生物学
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营养学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2019
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IF 8.063
Zhongyuan Chen,Yueting Peng,Xiaoxue Xie,Yi Feng,Tingting Li,Shun Li,Xiang Qin,Hong Yang,Chunhui Wu,Chuan Zheng,Jie Zhu,Fengming You,Yiyao Liu
Background & Aims : The use of antisense oligonucleotide-based nanosystems for the detection and regulation of tumor-related gene expression is thought to be a promising approach for cancer diagnostics and therapies. Herein, we report that a cubic-shaped iron oxide nanoparticle (IONC) core nanobeacon is capable of delivering an HSP90α mRNA-specific molecular beacon (HSP90-MB) into living cells and enhancing T 2 -weighted MR imaging in a tumor model. Methods : The nanobeacons were built with IONC, generation 4 poly(amidoamine) dendrimer (G4 PAMAM), Pluronic P123 (P123) and HSP90-MB labeled with a quencher (BHQ1) and a fluorophore (Alexa Fluor 488). Results : After internalization by malignant cells overexpressing HSP90α, the fluorescence of the nanobeacon was recovered, thus distinguishing cancer cells from normal cells. Meanwhile, MB-mRNA hybridization led to enzyme activity that degraded DNA/RNA hybrids and resulted in downregulation of HSP90α at both the mRNA and protein levels. Furthermore, the T 2 -weighted MR imaging ability of the nanobeacons was increased after PAMAM and P123 modification, which exhibited good biocompatibility and hemocompatibility. Conclusions : The nanobeacons show promise for applicability to tumor-related mRNA detection, regulation and multiscale imaging in the fields of cancer diagnostics and therapeutics.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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分子生物学
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医学成像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
·
IF 10.5
Xiaoxuan Wang,Fangxuan Li,Jialu Zhang,Lu Guo,Mengmeng Shang,Xiao Sun,Shan Xiao,Dandan Shi,Dong Meng,Yading Zhao,Chao Jiang,Jie Li
PD-1/PD-L1-based immune checkpoint blockade therapy has shown limited benefits in tumor patients, partially attributed to the inadequate infiltration of immune effector cells within tumors. Here, we established a nanoplatform named DPPA/IL-15 NPs to target PD-L1 for the tumor delivery of IL-15 messenger RNA (mRNA). DPPA/IL-15 NPs were endowed with ultrasound responsiveness and contrast-enhanced ultrasound (CEUS) imaging performance. They effectively protected IL-15 mRNA from degradation and specifically transfected it into tumor cells through the utilization of ultrasound-targeted microbubble destruction (UTMD). This resulted in the activation of IL-15-related immune effector cells while blocking the PD-1/PD-L1 pathway. In addition, UTMD could generate reactive oxygen species (ROS) that induce endoplasmic reticulum (ER) stress-driven immunogenic cell death (ICD), initiating anti-tumor immunity. In vitro and in vivo studies revealed that this combination therapy could induce a robust systemic immune response and enhance anti-tumor efficacy. Thus, this combination therapy has the potential for clinical translation through enhanced immunotherapy and provides real-time ultrasound imaging guidance.
研究领域:
肿瘤学
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免疫学
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纳米技术
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超声成像
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产品关联
DOI
PubMed
高影响因子
ELECTROPHORESIS
·
2026
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IF 2.5
Shang-Yin Wu,Yun-Jie He,Zhi-Jun Guo,Min Wang,Chang-Yun Xiong,Tingjun Hou,Bin Di,Wei-Jie Fang
mRNA-based vaccines and self-amplifying mRNA (saRNA) have gained growing attention for disease prevention and treatment, but precise detection of low-concentration RNA (including mRNA–lipid nanoparticles, mRNA–LNPs) stability and integrity remains challenging—limiting quality control of RNA-based therapeutics. Capillary electrophoresis (CE)-based instruments show potential, yet suitable concentration strategies for low-abundance, labile RNAs are lacking. This study established two distinct concentration methods (freeze-drying and ultrafiltration) applicable to mRNA, mRNA–LNPs, and saRNA formulations, enabling the conversion of dilute solutions to high-concentration preparations while preserving the structural and molecular integrity of the target nucleic acids. Subsequent stability evaluations and conventional high-performance liquid chromatography analyses of the concentrated products verified their superior storage stability and strong practical applicability. This article aims to reduce the difficulty of RNA integrity assessment and improve the accuracy of detecting various low-concentration RNA samples that may arise in the future.
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DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 8
·1725-1738
·
IF 7
Xin Sun,Xin Jiao,Zengguang Wang,Jie Ma,Tianchang Wang,Dan Zhu,Han Li,Liang Tang,Heyue Li,Changde Wang,Yiming Li,Chen Xu,Jinwu Wang,Yaogai Gan,Wenjie Jin
Cellular bioactivity and tissue regeneration can be affected by coatings on tissue-engineered scaffolds. Using mussel-inspired polydopamine (PDA) is a convenient and effective approach to surface modification. Therefore, 3D-printed β-tricalcium phosphate (β-TCP) scaffolds were coated with PDA in this study. The effects of the scaffolds on the adhesion and osteogenic differentiation of seeded bone marrow mesenchymal stem cells (BMSCs) in vitro and on new-bone formation in vivo were investigated. The potential mechanisms and related differential genes were assessed using mRNA sequencing. It was seen that PDA coating increased the surface roughness of the 3D-printed β-TCP scaffolds. Furthermore, it prompted the adhesion and osteogenic differentiation of seeded BMSCs. mRNA sequencing analysis revealed that PDA coating might affect the osteogenic differentiation of BMSCs through the calcium signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway, etc. Moreover, the expression of osteogenesis-related genes, such as R-spondin 1 and chemokine c-c-motif ligand 2, was increased. Finally, both the 3D-printed β-TCP scaffolds and PDA-coated scaffolds could significantly accelerate the formation of new bone in critical-size calvarial defects in rats compared with the control group; and the new bone formation was obviously higher in the PDA-coated scaffolds than in β-TCP scaffolds. In summary, 3D-printed β-TCP scaffolds with a PDA coating can improve the physicochemical characteristics and cellular bioactivity of the scaffold surface for bone regeneration. Potential differential genes were identified, which can be used as a foundation for further research.
研究领域:
生物材料
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组织工程
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干细胞生物学
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分子生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Yanhua Xu,Xue Tang,Zhaofei Guo,Yuwei Wang,Chunting He,Hongjiao Wei,Yuan Xue,Yangsen Ou,Lin Ye,Yuanhao Zhao,Kun Xiong,Guangsheng Du,Yunzhu Lin,Shuting Bai,Xun Sun
mRNA vaccines show great promise in cancer immunotherapy by eliciting potent cellular immune responses. Lipid nanoparticles (LNPs), validated through widespread use in COVID-19 vaccination, have become the most widely studied platform. However, their reliance on PEGylated lipids and tendency for hepatic accumulation may pose limitations for broader applications. To address these concerns, we developed a PEG-free nanoemulsion (NE) platform to deliver mRNA and minimize hepatic accumulation. We further employed a biomineralization strategy to anchor Mn 2+ onto human serum albumin (HSA), thereby mitigating the cytotoxicity of free Mn 2+ and forming a manganese-modified nanoemulsion (MnNE), which effectively activates the STING pathway. Compared with the LNP formulation of Moderna, MnNE showed superior transfection efficiency in antigen-presenting cells (APCs) following intramuscular injection. Using ovalbumin (OVA) as a model antigen, MnNE-mOVA elicited strong antigen-specific humoral and cellular immune responses. In both prophylactic and therapeutic E.G7-OVA tumor models, MnNE-mOVA significantly suppressed tumor growth and prolonged the survival compared with LNP-based formulations. Also, among all treatment groups, MnNE-mOVA most effectively reversed the immunosuppressive tumor microenvironment. These findings demonstrated that MnNE represented a safe and effective mRNA vaccine platform with substantial potential for cancer immunotherapy.
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2018
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IF 6.042
Xudong Wang,Jun Dai,Xuehong Min,Zhihua Yu,Yong Cheng,Kaixun Huang,Juliang Yang,Xiaoqing Yi,Xiaoding Lou,Fan Xia
Detection of an ultralow concentration of mRNA is important in the prognosis of gene-related diseases. In this study, a DNA-conjugated amphiphilic aggregation-induced emission probe (TPE-R-DNA) was synthesized for cancer tissue imaging and prognosis analysis based on an exonuclease III-aided target recycling technique. TPE-R-DNA comprise two components: a hydrophobic component that serves as the “turn-on” long wavelength fluorescence imaging agent (TPE-R-N3); and a hydrophilic single DNA strand (Alk-DNA) which acts as specific recognition part for target mRNA. In the absence of target mRNA, TPE-R-DNA had almost no fluorescence because of its high water solubility. Conversely, the TPE-R-DNA was digested by exonuclease III (Exo III) in the presence of MnSOD mRNA to release the hydrophobic fluorogens (TPE-R-AT). Subsequently, TPE-R-AT formed aggregates, and therefore, fluorescence signal was distinctly observed. For the first time, the structure of the hydrolysis product (TPE-R-AT), containing two bases A and T, was proved by the mass spectrum (MS) and high-performance liquid chromatography (HPLC). Moreover, the detection limit toward mRNA could be achieved in as low as 0.6 pM. Furthermore, the fluorescent signal can be used to confirm the MnSOD mRNA expression level in cancer tissue. The MnSOD mRNA expression in renal cancer was lower than in renal cancer adjacent tissue. In particular, the expression level was analyzed to predict prognosis of cancer patients. Our results demonstrate that a shorter survival time was evident among patients in lower MnSOD mRNA expression. Thereby, it indicates great potential for the development of an ultrasensitive biosensing platform for the application in disease prognosis.
研究领域:
癌症研究
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分子生物学
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
Cell and Bioscience
·
2021
·Vol. 11
·期 1
·1-16
·
IF 7.133
Xu Hongfei,Wang Zhen,Chen Miao,Zhao Wenting,Tao Tingting,Ma Liang,Ni Yiming,Li Weidong
Background Pathological cardiac hypertrophy is a major contributor of heart failure (HF), which seriously threatens human’s health world widely. Deregulation of m6A RNA methylation, and m6A methyltransferases and de-methyltransferases have been demonstrated to act essential roles in cardiac hypertrophy and HF. Here, we studied the potential roles and its underlying mechanisms of m6A Reader YTHDF proteins in HF. In this study, we constructed HF mouse model by transverse aortic constriction surgery. Primary cardiomyocytes were isolated and stimulated with isoproterenol (ISO) or phenylephrine (PHE) to induce myocardial hypertrophy.Results Through single-cell RNA-seq analysis, immunofluorescent staining, HE staining, Western blotting, and real time-PCR detections, we found that YTHDF2 mRNA and protein level, but not YTHDF1 or YTHDF3, was significantly increased during HF development. YTHDF2 overexpression could efficiently alleviate cardiac hypertrophy. Furthermore, through immunoprecipitation accompanied with mass spectrometry analysis, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that ISO stimulation did not evidently affect YTHDF2-interacting proteins. However, ISO or PHE stimulation significantly increased YTHDF2 protein interacting with Myh7 (beta-myosin heavy chain) mRNA, an important cardiac hypertrophy marker, in an m6A-dependent manner. Knockdown of Myh7 or deletion of the YTH domain of YTHDF2 reversed the protective effects of YTHDF2 on cardiac hypertrophy. Finally, we found that ISO or PHE stimulation promoted YTHDF2 protein expression through enhancing Ythdf2 mRNA stability in an m6A-dependent manner in cardiomyocytes.Conclusion sOverall, our results indicate that the m6A Reader YTHDF2 suppresses cardiac hypertrophy via Myh7 mRNA decoy in an m6A-dependent manner. This study highlights the functional importance of YTHDF2-dependent cardiac m6A mRNA regulation during cardiac hypertrophy, and provides a novel mechanistic insight into the therapeutic mechanisms of YTHDF2.
研究领域:
心脏病学
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分子生物学
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表观遗传学
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RNA生物学
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DOI
PubMed
高影响因子
Molecular Therapy-Nucleic Acids
·
2023
·
IF 8.8
Yufei Pan,Jing Guan,Yujing Gao,Yuejie Zhu,Huantong Li,Hua Guo,Qianyi He,Zhu Guan,Zhenjun Yang
Antisense oligonucleotides (ASOs) are a class of therapeutics targeting mRNAs or genes that have attracted much attention. However, effective delivery and optimal accumulation in target tissues in vivo are still challenging issues. CT102 is an ASO that targets IGF1R mRNA and induces cell apoptosis. Herein, a detailed exploration of the tissue distribution of ASOs delivered by liposomes was carried out. A formulation that resulted in increased hepatic accumulation was identified based on multiple intermolecular interactions between DCP (cytidinyl/cationic lipid DNCA/CLD and DSPE-PEG) and oligonucleotides, including hydrogen bonding, π-π stacking, and electrostatic interactions. The structurally optimized CT102s present a novel strategy for the treatment of hepatocellular carcinoma. The gapmer CT102 MOE5 and conjugate Glu-CT102 MOE5 showed superior antiproliferation and IGF1R mRNA suppression effects at 100 nM in vitro and achieved greater efficacy at a lower dose and administration frequency in vivo . Combined transcriptome and proteome analyses revealed that additional associated targets and functional regulations might simultaneously exist in ASO therapy. These results showed that a combination of lipid encapsulation and structural optimization in the delivery of oligonucleotide drugs has favorable prospects for clinical application.
研究领域:
分子生物学
·
肿瘤学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）