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Ionizable liposomal siRNA therapeutics enables potent and persistent treatment of Hepatitis B

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Signal Transduction and Targeted Therapy 2022年第3期7卷 802-815页

作者： Yuanyu Huang Shuquan Zheng Zhaoxu Guo Xavier de Mollerat du Jeu Xing-Jie liang Zhiwei Yang Hong-Yan Zhang Shan Gao zicai liang Suzhou Ribo Life Science Co.Ltd. Jiangsu 215300China Advanced Research Institute of Multidisciplinary Science School of Life ScienceSchool of Medical Technology(Institute of Engineering Medicine)Key Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Thermo Fisher Scientific CarlsbadCAUSA Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Chinese Academy of Sciences(CAS)National Center for Nanoscience and TechnologyBeijing 100190China

Small interfering RNA(siRNA)constitutes a promising therapeutic modality supporting the potential functional cure of hepatitis B.A novel ionizable lipidoid nanoparticle(RBP131)and a state-of-the-art lyophilization technology were developed in this study,enabling to deliver siRNA targeting apolipoprotein B(APOB)into the hepatocytes with an ED_(50)of 0.05 mg/kg after intravenous *** addition,according to the requirements of Investigational New Drug(IND)application,a potent siRNA targeting hepatitis B virus(HBV)was selected and encapsulated with RBP131 to fabricate a therapeutic formulation termed RB-HBV008.

关键词： injection APOB intravenous

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

Exogenous nucleic acids aggregate in non-P-body cytoplasmic granules when transfected into cultured cells

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Frontiers in Biology 2010年第3期5卷 272-281页

作者： Huang HUANG Na WEI Yingfei XIONG Feng YANG Huaqiang FANG Wenjun XIE Zhuan ZHOU Heping CHENG zicai liang Quan DU Institute of Molecular Medicine Peking UniversityBeijing 100871China Institute of Neurosciences The Fourth Military Medical UniversityXi'an 710032China

To modulate gene expression in research studies or in potential clinical therapies,transfection of exogenous nucleic acids including plasmid DNA and small interference RNA(siRNA)are generally ***,the cellular processing and the fate of these nucleic acids remain *** investigating the cellular behavior of transfected nucleic acids using confocal imaging,here we show that when siRNA was cotransfected into cultured cells with other nucleic acids,including single-stranded RNA oligonucleotides,single and double-stranded DNA oligonucleotides,as well as long double-stranded plasmid DNA,they all aggregate in the same cytoplasmic ***,the amount of siRNA aggregating in granules was found not to correlate with the gene silencing activity,suggesting that assembly of cytoplasmic granules triggered by siRNA transfection may be separable from the siRNA silencing *** results argue against the claim that the siRNAaggregating granules are the functional site of RNA interference(RNAi).Taken together,our studies suggest that,independent of their types or forms,extraneously transfected nucleic acids are processed through a common cytoplasmic pathway and trigger the formation of a new type of cytoplasmic granules“transfection granules”.

关键词： small interference RNA(siRNA) nucleic acids P-body RNA interference(RNAi) transfection

软件预测和MAST技术筛选mRNA反义核酸靶点的比较

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中国生物化学与分子生物学报 2004年第3期20卷 399-407页

作者：毛建平 zicai liang 毛秉智军事医学科学院放射医学研究所北京100850 Center for Genomics and Bioinformatics Karolinska InstitutetStockholm 17177瑞典

基因mRNA的结构靶点筛选是反义核酸药物研发的一个难题 .兔 (Oryctolaguscuniculus) β珠蛋白基因mRNA的结构靶位点通过运用MAST技术筛选获得 ,和计算机软件RNAstructure3 71模拟分析的位点进行了比较 ,也和寡核苷酸微阵列杂交技术筛选... 详细信息

基因mRNA的结构靶点筛选是反义核酸药物研发的一个难题 .兔 (Oryctolaguscuniculus) β珠蛋白基因mRNA的结构靶位点通过运用MAST技术筛选获得 ,和计算机软件RNAstructure3 71模拟分析的位点进行了比较 ,也和寡核苷酸微阵列杂交技术筛选获得的靶点结果 (M .Natalie ,1 997)进行了比较 ,显示 :据MAST技术获得的兔 β珠蛋白基因 2个反义核酸结合靶位点 ,和用RNAstructure3 71软件给出的模拟分析的 2个靶位点相同 ,且它们与寡核苷酸微阵列杂交技术的结果完全一致 .运用MAST技术筛选获得绿色荧光蛋白 (GFP)mRNA有 4个结构靶位点 ,体外分析表明这 4个靶位点均有效 ,其中有 3个与RNAstructure3 71软件分析的靶点相同 ,但计算机模拟推荐的结构靶位点较多 ,而且随着基因长度增加确认靶位点的难度增大 ,获得的靶位点还需要实验验证 ,计算机软件模拟分析对实验筛选靶点、设计反义核酸有辅助价值 .MAST方法能筛选各种长度基因mRNA的全部可及位点和准确给定核苷酸的起止位置以供设计反义核酸 ,具有简单快捷的优点 ,将能为反义核酸设计起重要作用 .

关键词： mRNA RNAstructure3.71 MAST β珠蛋白 GFP 可及位点反义核酸

AQR is a novel type 2 diabetes-associated gene that regulates signaling pathways critical for glucose metabolism

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Journal of Genetics and Genomics 2018年第2期45卷 111-120页

作者： Chun Song Han Yan Hanming Wang Yan Zhang Huiqing Cao Yiqi Wan Lingbao Kong Shenghan Chen Hong Xu Bingxing Pan Jin Zhang Guohuang Fan Hongbo Xin zicai liang Weiping Jia Xiao-Li Tian Laboratory of Human Population Genetics Institute of Molecular Medicine Peking University Beijing 100871 China State Key Laboratory of Membrane Biology Institute of Molecular Medicine Peking University Beijing 100871 China Beijing Key Laboratory of Cardiometabolic Molecular Medicine Peking University Beijing 100871 China Laboratory of Nucleic Acid Technology Institute of Molecular Medicine Peking University Beijing 100871 China Human Population Genetics Human Aging Research Institute and School of Life Sciences Nanchang University Nanchang 330006 China Institute of Life Science and School of Life Science Nanchang University Nanchang 330031 China School of Basic Medical Sciences Nanchang University Nanchang 330006 China Institute of Translational Medicine Nanchang University Nanchang 330031 China Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai 200233 China

Type 2 diabetes mellitus（T2 DM） is a common metabolic disease influenced by both genetic and environmental factors. In this study, we performed an in-house genotyping and meta-analysis study using three independent GWAS datasets of T2 DM and found that rs3743121, located 1 kb downstream of AQR,was a novel susceptibility SNP associated with T2 DM. The risk allele C of rs3743121 was correlated with the increased expression of AQR in white blood cells, similar to that observed in T2 DM models. The knockdown of AQR in HepG2 facilitated the glucose uptake, decreased the expression level of PCK2,increased the phosphorylation of GSK-3β, and restored the insulin sensitivity. Furthermore, the suppression of AQR inhibited the mTOR pathway and the protein ubiquitination process. Our study suggests that AQR is a novel type 2 diabetes-associated gene that regulates signaling pathways critical for glucose metabolism.

关键词： Type 2 diabetes AQR Glucose metabolism Ubiquitination

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一种基于计算机仿真的自动化生产线改进方法

信息与电脑 2019年第17期31卷 4-5页

作者：梁子财华中科技大学中欧清洁与可再生能源学院

随着“中国制造2025”战略的提出与实施,工业自动化生产线在其中发挥着至关的作用。目前,许多自动化生产线都存在生产效率低下、设备利用率低、生产物流堵塞等问题,严重制约企业的生产效益。笔者提出了一种基于计算机仿真技术的自动化... 详细信息

随着“中国制造2025”战略的提出与实施,工业自动化生产线在其中发挥着至关的作用。目前,许多自动化生产线都存在生产效率低下、设备利用率低、生产物流堵塞等问题,严重制约企业的生产效益。笔者提出了一种基于计算机仿真技术的自动化生产线改进方法,既能用于设计新的生产线,也能用于改造现有的生产线。

关键词：自动化生产线生产线改进计算机仿真技术设备利用率

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数控加工G代码程序三维加工仿真软件开发

信息与电脑 2019年第17期31卷 57-59页

作者：梁子财华中科技大学中欧清洁与可再生能源学院

笔者利用Qt平台与OpenGL库开发了一款针对数控加工G代码程序的三维加工仿真软件。该软件能够根据加载的G代码程序提取加工图像点位信息并绘制加工图像并且可以模拟刀具的加工过程,同时可以检测G代码程序的错误并给出错误信息,方便用户... 详细信息

笔者利用Qt平台与OpenGL库开发了一款针对数控加工G代码程序的三维加工仿真软件。该软件能够根据加载的G代码程序提取加工图像点位信息并绘制加工图像并且可以模拟刀具的加工过程,同时可以检测G代码程序的错误并给出错误信息,方便用户提前验证G代码的可行性。通过使用该软件,技术人员无须试加工就可以验证G代码的加工效果,从而能减少资源浪费与缩短开发周期。

关键词： Qt OpenGL G代码 G代码程序加工仿真

Identification of novel cell proliferation-enhancing genes by random siRNA library screening

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Identification of novel cell proliferation-enhancing genes b...

基于QT on Android的手机版伺服参数调试平台开发

中国生物化学与分子生物学会第十届会员代表大会暨全国学术会议

作者： Yuan Xiong Cuiqing Fan Ning Zhu Yabin Lu Jiewen Zhang Song Wang zicai liang Yan Shen Meihong Chen Institute of Basic Medical Sciences Chinese Academy of Medical Sciences(CAMS)/ School of Basic MedicinePeking Union Medical College(PUMC)National Laboratory of Medical Molecular Biology Institute of Molecular Medicine Peking University

RNA interference(RNAi) has become a powerful research tool in functional genomics *** have previously reported the construction of a random small interfering RNA (siRNA) *** library is versatile as it avoids siRNA sequence bias,and targets both known and unknown genes. Here we report a high throughput screening with this random siRNA library to reveal novel genes that can accelerate preosteoblast MC3T3-E1 cell *** siRNAs that enhance MC3T3-E1 cell proliferation were identified.

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信息与电脑 2019年第16期31卷 87-90页

作者：梁子财华中科技大学中欧清洁与可再生能源学院

伺服驱动系统的性能对工况变化十分敏感,在实际应用前需要进行驱动器和电机的参数配置、增益调整等工作。参数调整工作复杂,且驱动器面板设置操作困难,对调整人员的专业水平要求高。若未经合适的参数调整便投入使用,则无法有效发挥设计... 详细信息

伺服驱动系统的性能对工况变化十分敏感,在实际应用前需要进行驱动器和电机的参数配置、增益调整等工作。参数调整工作复杂,且驱动器面板设置操作困难,对调整人员的专业水平要求高。若未经合适的参数调整便投入使用,则无法有效发挥设计性能。针对伺服驱动器参数调整复杂的问题,笔者开发了一款基于QT on Android的具有配置驱动器及电机参数、智能监测伺服系统性能等功能的手机版伺服调整平台,用户可以利用该平台对伺服参数进行调整与监控,操作简便。

关键词： Qt on Android 伺服参数调整伺服驱动器手机软件