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Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle

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Bioactive Materials 2020年第4期5卷 1053-1061页

作者： Tongren Yang Chunhui Li Xiaoxia Wang deyao zhao Mengjie Zhang Huiqing Cao Zicai Liang Haihua Xiao Xing-Jie Liang Yuhua Weng Yuanyu Huang School of Life Science Advanced Research Institute of Multidisciplinary ScienceInstitute of Engineering MedicineKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing100081China Institute of Molecular Medicine Peking UniversityBeijing100871China Suzhou Ribo Life Science Co.Ltd. Jiangsu215300China Beijing National Laboratory for Molecular Science State Key Laboratory of Polymer Physical and ChemistryInstitute of ChemistryChinese Academy of ScienceBeijing100190China Chinese Academy of Sciences(CAS)Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing100190China School of Materials and the Environment Beijing Institute of TechnologyZhuhai519085China Department of Radiation Oncology The First Affiliated Hospital of Zhengzhou UniversityErqiZhengzhou450000China

mRNA is a novel class of therapeutic modality that holds great promise in vaccination,protein replacement therapy,cancer immunotherapy,immune cell engineering ***,optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad *** we present an ionizable lipid nanoparticle(iLNP)based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized *** encoding luciferase or erythropoietin(EPO)were prepared by in vitro transcription and formulated with proposed iLNP,to form iLP171/mRNA *** was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and *** maximum amount of protein expression was found at 6 h *** expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized ***,no toxicity or immunogenicity was observed for these mRNA ***,our study provides a useful and promising platform for mRNA therapeutic development.

关键词： mRNA therapy Lipid nanoparticle mRNA delivery Erythropoietin Codon optimization

Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy

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Bioactive Materials 2022年第3期7卷 590-601页

作者： Chunhui Li Tongren Yang Yuhua Weng Mengjie Zhang deyao zhao Shuai Guo Bo Hu Wanxuan Shao Xiaoxia Wang Abid Hussain Xing-Jie Liang Yuanyu Huang School of Life Science Advanced Research Institute of Multidisciplinary ScienceInstitute of Engineering MedicineKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing100081China Department of Radiation Oncology The First Affiliated Hospital of Zhengzhou UniversityErqiZhengzhou450000China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing100871China Chinese Academy of Sciences(CAS)Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing100190China School of Materials and the Environment Beijing Institute of TechnologyZhuhai519085China

CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool,that relies on Cas9 protein and single guided RNA(sgRNA)to edit target ***,the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical ***,we report an ionizable lipid nanoparticle(iLP181,pKa=6.43)based on iLY1809 lipid enabling robust gene editing in vitro and in *** iLP181 effectively encapsulate psgPLK1,the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1(PLK1).The iLP181/psgPLK1 nanoformulation showed uniformity in size,regular nanostructure and nearly neutral zeta potential at pH *** nanoformulation effectively triggered editing of PLK1 gene with more than 30%efficiency in HepG2-Luc ***181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous *** addition,it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA,without inducing adverse effects to the main organs including the liver and *** study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system(even other bioactive molecules),but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes.

关键词： CRISPR/Cas Gene editing Lipid nanoparticle PLK1 Cancer therapy

Lipid-conjugated siRNA hitchhikes endogenous albumin for tumor immunotherapy

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Chinese Chemical Letters 2023年第11期34卷 202-208页

作者： Bo Hu Sudong Kong Yuhua Weng deyao zhao Abid Hussain Qingze Jiao Shijing Zhan Ling Qiu Jianguo Lin Minhao Xie Bo Li Yuanyu Huang School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Key Laboratory for Separation and Analysis in Biomedicine and PharmaceuticalsBeijing Institute of TechnologyBeijing 100081China School of Chemical and Material Engineering Jiangnan UniversityWuxi 214122China NHC Key Laboratory of Nuclear Medicine Jiangsu Key Laboratory of Molecular Nuclear MedicineJiangsu Institute of Nuclear MedicineWuxi 214063China Department of Radiation Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China School of Materials and the Environment Beijing Institute of TechnologyZhuhai 519085China Rigerna Therapeutics Suzhou 215127China

With the development of a small interfering RNA(siRNA)delivery strategy,increasing siRNA therapeutics for tumor treatment appeared in clinical trials and pre-clinical ***,the test results of such therapeutics unveiled that efficient siRNA delivery to tumor tissues is still *** is considered an ideal carrier for delivering hydrophobic agents into tumor tissue because it is highly concentrated and long-circulating in blood and has propensity of tumor ***,we synthesized lipid conjugated siRNAs(LsiRNAs),which showed high affinity to ***,LsiRNAs non-covalently bind to the hydrophobic core of albumin through its octadecyl *** small size of albumin/LsiRNAs allows the complex to penetrate tumor tissue *** test proved that albumin extremely prolonged circulation time and increased tumor retention of associated ***,LsiRNA against programmed death ligand-1(Pdl1)efficiently suppressed tumor growth as well as prolonged survival time of tumor bearing mice by increasing infiltration of CD8^(+)T cells as well as promoted the maturation of dendritic cells both in tumor and ***,LsiRNAs provide a simple but effective way for siRNA tumor delivery that“hitchhikes”on albumin.

关键词： Albumin siRNA Lipid conjugate Tumor treatment Immunotherapy

维普期刊数据库

Research on Software System for Training Simulator of Vessel Nuclear-Powered plant

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Research on Software System for Training Simulator of Vessel...

Recycling arsenic-containing bio-leaching residue after thermal treatment in cemented paste backfill:Structure modification,binder properties and environmental assessment

第二届21世纪和谐核电系统国际会议（ISSNP2008）

作者： Zhang Xin,Li Jianfei,Lian Haibo,and zhao deyao Training Department,Navy submarine Institute,266042,china

This text introduce the development environment of vessel nuclear-poweredsetting simulator operator,design methods and the communication mechanism of the *** development environment for software system,carry on a comparison to two kinds of operate systems:Windows system and Unix *** comparison,consider that the Windows system is the development trend of simulation system *** the soft simulation,this text considers that intouch configuration software has better applied foreground, introduce the main software for development of simulation in the meantime;introduce request to software system for the tranning simulation of vessel nuclear-powered setting,and main applied *** request includes:the mold piece turns,enlargement, proceed together a processing and permit a wrong *** main software has:the object process characteristic imitates simulation software package,the software package of management monitoring,data acquisition software,graph processing software package, database management *** the design methods,this text consider that should be realizes the following requests:initialization of simulator condition,the surveillance appearance,parameter,sketch and chart manifestation,simulator breakdown constitution,freeze, defrost,heavy hold,heavy put,quick hour,slow hour,record simulator running status and parameter change *** the communication mechanism,this text considers that the outer computers such as main computers,teacheing control computers and the labor controls machine etc link together through a high-speed ether net,constituting a local area *** communication agreement adopts the Dynamic Data Exchang of *** the software system,its advantage is that man-machine interface is friendly,the true feeling is strong,the simulator run stably,can carry out the request of whole scopeses,overall dimension,entire process trainning.

关键词： Nuclear-powered Setting Simulator Software

来源： cnki会议评论

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International Journal of Minerals,Metallurgy and Materials 2024年第10期31卷 2136-2147页

作者： Dengfeng zhao Shiyu Zhang Yingliang zhao Department of Mining Engineering Lyuliang UniversityLvliang 033000China School of Civil and Environmental Engineering University of Science and Technology BeijingBeijing 100083China School of Mining Engineering Taiyuan University of TechnologyTaiyuan 030024China Department of Civil and Environmental Engineering The Hong Kong Polytechnic UniversityHong Kong 00852China

The substantial arsenic(As)content present in arsenic-containing bio-leaching residue(ABR)presents noteworthy environ-mental challenges attributable to its inherent instability and susceptibility to *** its elevated calcium sulfate content,ABR exhibits considerable promise for industrial *** study delved into the feasibility of utilizing ABR as a source of sulfates for producing super sulfated cement(SSC),offering an innovative binder for cemented paste backfill(CPB).Thermal treatment at varying temperatures of 150,350,600,and 800℃ was employed to modify ABR’s *** investigation encompassed the examination of phase transformations and alterations in the chemical composition of As within ***,the hydration characteristics of SSC utilizing ABR,with or without thermal treatment,were studied,encompassing reaction kinetics,setting time,strength development,and *** findings revealed that thermal treatment changed the calcium sulfate structure in ABR,consequently impacting the resultant sample ***,calcination at 600℃ demonstrated optimal modification effects on both early and long-term strength *** enhanced performance can be attributed to the augmented formation of reaction products and a densified ***,the thermal treatment elicited modifications in the chemical As fractions within ABR,with limited impact on the As immobilization capacity of the prepared binders.

关键词： cemented paste backfill bio-leaching residue arsenic immobilization binder hydration calcination

维普期刊数据库

Automatic modeling algorithm of stochastic error for inertial sensors

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Control Theory and Technology 2024年第1期22卷 81-91页

作者： Luodi zhao Long zhao School of Automation Science and Electrical Engineering Beihang UniversityBeijing100191China Digital Navigation Center Beihang UniversityBeijing100191China Science and Technology on Aircraft Control Laboratory Beihang UniversityBeijing100191China

This paper proposes an automatic algorithm to determine the properties of stochastic processes and their parameters for inertial error. The proposed approach is based on a recently developed method called the generalized method of wavelet moments (GMWM), whose estimator was proven to be consistent and asymptotically normally distributed. This algorithm is suitable mainly (but not only) for the combination of several stochastic processes, where the model identification and parameter estimation are quite difficult for the traditional methods, such as the Allan variance and the power spectral density analysis. This algorithm further explores the complete stochastic error models and the candidate model ranking criterion to realize automatic model identification and determination. The best model is selected by making the trade-off between the model accuracy and the model complexity. The validation of this approach is verified by practical examples of model selection for MEMS-IMUs (micro-electro-mechanical system inertial measurement units) in varying dynamic conditions.

关键词： GMWM Stochastic process Inertial sensor Sensor calibration Error model Allan variance

Meeting the challenges of invasive alien species

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National Science Review 2024年第3期11卷 296-298页

作者： Weijie zhao NSR news

The Xinjiang Uygur Autonomous Region of China is famous for its tomato production. Abundant sunshine, large day–night temperature difference and the abundant irrigation by snowmelt from the Tianshan Mountains produce...

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Ling-Ling Chen: RNA has its own features;don't study it as a protein

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National Science Review 2024年第2期11卷 301-305页

作者： Weijie zhao NSR

Non-coding RNA(ncRNA) has been a very active research area over the past 30 years. From small nc RNA – the discovery of RNA interference won the lead researchers the Nobel Prize, to long ncRNA(lncRNA), which has attracted much attention in recent years, various nc RNAs participate in all kinds of biological processes and show a variety of biomedical application prospects.

关键词： RNA

Giant Flexoelectric Effect in Snapping Surfaces Enhanced by Graded Stiffness

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Acta Mechanica Solida Sinica 2024年第4期37卷 528-540页

作者： Chuo zhao Department of Aeronautics Imperial College LondonSouth Kensington CampusLondonSW72AZUK

Flexoelectricity is present in nonuniformly deformed dielectric materials and has size-dependent properties, making it useful for microelectromechanical systems. Flexoelectricity is small compared to piezoelectricity;therefore, producing a large-scale flexoelectric effect is of great interest. In this paper, we explore a way to enhance the flexoelectric effect by utilizing the snap-through instability and a stiffness gradient present along the length of a curved dielectric plate. To analyze the effect of stiffness profiles on the plate, we employ numerical parameter continuation. Our analysis reveals a nonlinear relationship between the effective electromechanical coupling coefficient and the gradient of Young’s modulus. Moreover, we demonstrate that the quadratic profile is more advantageous than the linear profile. For a dielectric plate with a quadratic profile and a modulus gradient of − 0.9, the effective coefficient can reach as high as 15.74 pC/N, which is over three times the conventional coupling coefficient of piezoelectric material. This paper contributes to our understanding of the amplification of flexoelectric effects by harnessing snapping surfaces and stiffness gradient design.

关键词： Functionally graded material Flexoelectricity Numerical continuation Snap-through instability