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| 1 | Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle显示文摘mRNA is a novel class of therapeutic modality that holds great promise in vaccination,protein replacement therapy,cancer immunotherapy,immune cell engineering etc.However,optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application.Here we present an ionizable lipid nanoparticle(iLNP)based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized mRNAs.mRNAs encoding luciferase or erythropoietin(EPO)were prepared by in vitro transcription and formulated with proposed iLNP,to form iLP171/mRNA formulations.It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes.The maximum amount of protein expression was found at 6 h post-administration.The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA.Moreover,no toxicity or immunogenicity was observed for these mRNA formulations.Therefore,our study provides a useful and promising platform for mRNA therapeutic development. | Tongren Yang Chunhui Li Xiaoxia Wang Deyao Zhao Mengjie Zhang Huiqing Cao Zicai Liang Haihua Xiao Xing-Jie Liang Yuhua Weng Yuanyu Huang | 2020 | Bioactive Materials2020，5，4： | 7 |
| 2 | 软件预测和MAST技术筛选mRNA反义核酸靶点的比较显示文摘基因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 . | 毛建平 Zicai LIANG 毛秉智 | 2004 | 中国生物化学与分子生物学报2004，20，3： | 4 |
| 3 | AQR is a novel type 2 diabetes-associated gene that regulates signaling pathways critical for glucose metabolism显示文摘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. | 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 | 2018 | Journal of Genetics and Genomics2018，45，2： | 1 |
| 4 | Circulating microRNA-122 as a potential biomarker for liver injury显示文摘 | Xianfeng Ding Jianv Ding Jing Ning Fan Yi Jiankui Chen Deyao Zhao Jiaping Zheng Zicai Liang Zhiyuan Hu Quan Du | 2012 | Molecular Medicine Reports2012，，6： | 1 |
| 5 | Rising from Ashes:Non-Coding RNAs Come of Age显示文摘It was recognized that a majority of the whole human genome is transcribed but only about 2%of genome actually encode all the proteins that were supposed,according to the central dogma,executing most of the biological functions of an organism.At an age proteins dominate,over 90%nonprotein coding regions were long regarded as trash,but nevertheless it was puzzling why god would allocate such a big portion of a genome to things without obvious meanings, | Zicai Liang Xiu-Jie Wang | 2013 | Journal of Genetics and Genomics2013，40，4： | 1 |
| 6 | Modification of the siRNA Passenger Strand by 5‐Nitroindole Dramatically Reduces its Off‐Target Effects显示文摘 | Junbin Zhang Jie Zheng Chang Lu Quan Du Zicai Liang Zhen Xi | 2012 | ChemBioChem2012，，13： | 1 |
| 7 | Ionizable liposomal siRNA therapeutics enables potent and persistent treatment of Hepatitis B显示文摘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 injection.In 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. | Yuanyu Huang Shuquan Zheng Zhaoxu Guo Xavier de Mollerat du Jeu Xing-Jie Liang Zhiwei Yang Hong-Yan Zhang Shan Gao Zicai Liang | 2022 | Signal Transduction and Targeted Therapy2022，7，3： | 1 |
| 8 | Hypoxia-Independent Angiogenesis in Adipose Tissues during Cold Acclimation显示文摘 | Yuan Xue Natasa Petrovic Renhai Cao Ola Larsson Sharon Lim Shaohua Chen Helena M. Feldmann Zicai Liang Zhenping Zhu Jan Nedergaard Barbara Cannon Yihai Cao | 2009 | Cell Metabolism2009，，1： | 1 |
| 9 | Exogenous nucleic acids aggregate in non-P-body cytoplasmic granules when transfected into cultured cells显示文摘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 performed.However,the cellular processing and the fate of these nucleic acids remain elusive.By 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 granules.Interestingly,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 event.Our 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”. | Huang HUANG Na WEI Yingfei XIONG Feng YANG Huaqiang FANG Wenjun XIE Zhuan ZHOU Heping CHENG Zicai LIANG Quan DU | 2010 | Frontiers in Biology2010，5，3： | 0 |
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