Abstract：
AIM:Our previous study demonstrated an siRNA-mediated, allele-specific silencing of mutant genes that cause amyotrophic lateral sclerosis. To improve siRNA design for better therapeutic use of RNA interference, we systematically tested the base-pairing mismatch strategy in the design of asymmetric siRNA. METHODS:A naturally symmetric siRNA that targets the human Cu Zn superoxide dismutase G85R mutant allele was modified by placing either 1 or 2 mismatches at the end of the siRNA from position 1 to 4 at each time. The target preference and silencing efficacy of modified siRNA were measured using a modified dual luciferase system. RESULTS:The modification of single base-pairing mismatch successfully achieved the conversion of the siRNA that was originally favored to the antisense of the mutant allele to the one that was favored to the sense strand of the gene. Compared to the single-mismatched siRNA, those with double-mismatch at one end demonstrated an increased asymmetry, and thus, an enhanced specificity and efficacy of gene silencing. In addition, the siRNA with double-mismatch at both ends remained in symmetry. CONCLUSION:Our results suggest the effectiveness of converting a symmetric siRNA to an asymmetric one by introducing mismatches into its structure, and the superiority of double-mismatched siRNA to single-mismatched siRNA in producing selective gene silencing resulting from the disruption of siRNA symmetry. The double-mismatch strategy is an improvement of the single-mismatch method and could be useful in the design of effective siRNAs for the treatment of diseases caused by dominant, gain-of-function gene mutations, such as ALS.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Geng CM,Ding HLdoi
10.1111/j.1745-7254.2008.00740.xsubject
Has Abstractpub_date
2008-02-01 00:00:00pages
211-6issue
2eissn
1671-4083issn
1745-7254journal_volume
29pub_type
杂志文章abstract：AIM:To investigate effects of CpG oligodeoxynucleotide (CpG ODN) on the mRNA expression of transcription factors GATA binding protein 3 (GATA-3) and T-box expressed in T cells (T-bet) in asthmatic mice. METHODS:An asthmatic mouse model was established and treated with CpG ODN. Total inflammatory cells and eosinophils ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00157.x
更新日期：2005-09-01 00:00:00
abstract：AIM:To construct a recombinant adenovirus that can express human spermidine/ spermine N1-acetyltransferase (SSAT) and detect its inhibitory effect on colorectal cancer cell growth in vitro. METHODS:A 516 bp cDNA of SSAT was amplified and cloned into a pGL3-hTERT plasmid. The pGL3-hTERT-SSAT recombinant was digested, a...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00779.x
更新日期：2008-05-01 00:00:00
abstract：AIM:To investigate the effect of 7-hydroxystaurosporine (UCN-01), a selective protein kinase C (PKC) inhibitor, on cell growth, migration, and invasion in invasive human glioblastoma U-87MG cells. METHODS:PKC activity was determined based on the PKC-catalyzed transfer of the (32)P-phosphate group from [g-(32)P]ATP int...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00087.x
更新日期：2005-04-01 00:00:00
abstract：:As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capaci...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/s41401-020-0415-5
更新日期：2020-07-01 00:00:00
abstract：:Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are m...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2015.24
更新日期：2015-06-01 00:00:00
abstract：:The chemokine receptor CCR5 is an important anti-HIV (human immunodeficiency virus) drug target owning to its pivotal role in HIV-1 viral entry as a co-receptor. Here, we present a 2.9 Å resolution crystal structure of CCR5 bound to PF-232798, a second-generation oral CCR5 antagonist currently in phase II clinical tri...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0054-2
更新日期：2019-04-01 00:00:00
abstract：:Hepatic fibrosis is a disease characterized by excessive deposition of extracellular matrix (ECM) in the liver. Activation of hepatic stellate cells (HSCs) is responsible for most of ECM production. Oxidative stress and reactive oxygen species (ROS) may be important factors leading to liver fibrosis. NADPH oxidase 4 (...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-00545-9
更新日期：2020-10-28 00:00:00
abstract：AIM:To study the effects of cimetidine (Cim) on the production of interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) by splenocytes in immune-derived aplastic anemic (AA) mice. METHODS:Aplastic anemic mice model was constructed first, and then the splenocytes were induced to secrete IFN gamma and...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：AIM:To establish a population pharmacokinetics (PPK) model for lamotrigine (LTG) in Chinese children with epilepsy in order to formulate an individualized dosage guideline. METHODS:LTG steady-state plasma concentration data from therapeutic drug monitoring (TDM) were collected retrospectively from 284 patients, with a...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.118
更新日期：2012-11-01 00:00:00
abstract：AIM:To investigate the immunoregulatory functions of water extracts of Hericium erinaceum (WEHE) focusing on natural killer (NK) cell-based anticancer activities. METHODS:Mouse splenocytes or purely isolated NK cells were stimulated with 1-100 mg/L WEHE for 24 h followed by co-culture with (51)Cr-labeled Yac-1 cells f...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00577.x
更新日期：2007-06-01 00:00:00
abstract：AIM:The pro-fibrogenic cytokine transforming growth factor-beta 1 (TGF-beta1) has attracted much attention for its potential role in the etiology of idiopathic pulmonary fibrosis (IPF). Here, we demonstrate that MS80, a novel sulfated oligosaccharide extracted from seaweed, can bind TGF-beta1. The aim of the present st...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2009.86
更新日期：2009-07-01 00:00:00
abstract：AIM:To investigate the effect of epigallocatechin gallate (EGCG) on angiotensin II (Ang II)-induced stress fiber formation and hyperpermeability in endothelial cells. METHODS:Human umbilical vein endothelial cells (HUVECs) were treated with Ang II in the absence or presence of EGCG or mitogen-activated protein kinases...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.75
更新日期：2010-10-01 00:00:00
abstract：:Alternative splicing is a key process of multi-exonic gene expression during pre-mRNA maturation. In this process, particular exons of a gene will be included within or excluded from the final matured mRNA, and the resulting transcripts generate diverse protein isoforms. Recent evidence demonstrates that approximately...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2015.43
更新日期：2015-10-01 00:00:00
abstract：AIM:To characterize the in vitro bioactivities of rhodanine derivatives as novel peroxisome proliferator-activated receptor (PPAR) gamma modulators, based on a hit (SH00012671) identified during high-throughput screening (HTS) of a diverse synthetic compound library, and to preliminarily elucidate the structure-activit...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2007-12-01 00:00:00
abstract：:The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells. Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells. Artesunate, a derivative of artemisinin, displays broad antitumor activity and direct cytotoxicity on va...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-0445-z
更新日期：2020-07-23 00:00:00
abstract：:Propofol is a commonly used intravenous anesthetic agent, which has been found to affect cell survival and proliferation especially in early life. Our previous studies show that propofol-induced neurodegeneration and neurogenesis are closely associated with cell autophagy. In the present study we explored the roles of...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0303-z
更新日期：2020-03-01 00:00:00
abstract：:Pre-B-cell leukemia transcription factor 3 (PBX3) is a member of the PBX family and contains a highly conserved homologous domain. PBX3 is involved in the progression of gastric cancer, colorectal cancer, and prostate cancer; however, the detailed mechanism by which it promotes tumor growth remains to be elucidated. H...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-00599-9
更新日期：2021-02-01 00:00:00
abstract：:Antimony, a natural element that has been used as a drug for over more than 100 years, has remarkable therapeutic efficacy in patients with acute promyelocytic leukemia. This review focuses on recent advances in developing antimony anticancer agents with an emphasis on antimony coordination complexes, Sb (III) and Sb ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1111/j.1745-7254.2008.00818.x
更新日期：2008-08-01 00:00:00
abstract：:Oral administration of curcumin has been shown to inhibit pulmonary fibrosis (PF) despite its extremely low bioavailability. In this study, we investigated the mechanisms underlying the anti-PF effect of curcumin in focus on intestinal endocrine. In bleomycin- and SiO2-treated mice, curcumin (75, 150 mg· kg-1 per day)...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-0469-4
更新日期：2020-07-21 00:00:00
abstract：:Innovative teaching methodologies in different parts of the world are being practiced since last 3 decades. The aim of this review is to report the transition from traditional to innovative self learning process in Ziauddin Medical University, a new medical institute of Pakistan. Various problems encountered have been...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-09-01 00:00:00
abstract：AIM:To investigate molecular mechanism of testis development and spermatogenesis. METHODS:A human testis cDNA microarray was hybridized with probes from human adult testis, embryo testis and human sperm, and the differential expressed clones were sequenced and analyzed. Expression of PIAS-NY gene was analyzed by RT-PC...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-08-01 00:00:00
abstract：AIM:To investigate the actions of the muscarinic agonist carbachol on glutamate-induced neurotoxicity in PC12 cells, and the underlying mechanisms. METHODS:PC12 cells were treated with different concentrations of glutamate for 24 or 48 h. The cell viability was measured using MTT assay, and the expression and activati...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.42
更新日期：2013-07-01 00:00:00
abstract：AIM:To study the effects of dl-praeruptorin A (Pd-Ia) on nucleus factor-kappaB (NF-kappaB) activativity and tumor necrosis factor-alpha (TNF-alpha) expression in ischemia-reperfusion (I/R) myocardium. METHODS:Langendorff's isolated rat heart was subjected to a 10-min ischemia followed by a 30-min reperfusion. NF-kappa...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-01-01 00:00:00
abstract：:Specific chromosome aberrations are frequently detected during the development of hepatocellular carcinoma. Molecular cytogenetic approaches such as comparative genomic hybridization and loss of heterozygosity analyses have provided fruitful information on changes in HCC cases at the genomic level. Mapping of chromoso...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1111/j.1745-7254.2005.00126.x
更新日期：2005-06-01 00:00:00
abstract：AIM:To study the protective effect of the polypeptide isolated from Chlamys farreri (PCF) on hairless mice skin damaged by ultraviolet A. METHODS:Enzymes and malondialdehyde (MDA) were determined by biochemical methods; the expressions of Bcl-2 protein and NOS protein were examined by immunohistochemical technique. Th...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-09-01 00:00:00
abstract：AIM:To study the neurotoxicity and toxicokinetics of norfloxacin (NFLX) in freely moving rats. METHODS:Rats were assigned randomly to four treatment groups that received a single iv dose of 50, 100, 200 mg/kg of NFLX and 0.9 % saline, respectively. Electroencephalogram (EEG) was continuously recorded with a computeriz...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-06-01 00:00:00
abstract：AIM:To develop a novel, in situ gel system for nasal delivery of scopolamine hydrobromide (SCOP) and study its efficacy on motion sickness. METHODS:SCOP in situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in terms of viscosity, in vitro release, and nasal ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00540.x
更新日期：2007-04-01 00:00:00
abstract：AIM:Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo. METHODS:Cell proliferation, DNA fragmentation, Ann...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2014.15
更新日期：2014-06-01 00:00:00
abstract：:A comparison of the cardiovascular actions of the extract of Radix Stephaniae Tetrandrae (RST), the root of a Chinese hero Stephania tetrandra S Moore, in rats with those of tetrandrine (Tet), the best known active component of RST was reviewed. The RST extract inhibits Ca2+ influx into the myocyte and reduces protein...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：
更新日期：2000-12-01 00:00:00
abstract：:Cancer metastasis is responsible for over 90% of breast cancer-related deaths, and inhibiting lymph node metastasis is an option to treat metastatic disease. Herein, we report the use of IR-780-loaded polymeric micelles (IPMs) for effective photothermal therapy (PTT) of breast cancer lymphatic metastasis. The IPMs wer...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.109
更新日期：2018-01-01 00:00:00
