Abstract:
:Antisense technology exploits oligonucleotide analogs to bind to target RNAs via Watson-Crick by hybridization. Once bound, the antisense agent either disables or induces the degradation of the target RNA. Antisense agents may also be used to alter splicing. Developing antisense technology involves the creation of a new pharmacology. The receptors, pre- and mRNAs, had never been studied before as sites for drug binding and action. The drugs, oligonucleotide analogs, had never made or tested as drugs before and no medicinal chemistry had been performed. The receptor binding mechanism, Watson-Crick hybridization had never been demonstrated as feasible to exploit from a pharmacological perspective. The post-receptor binding events were literally unknown and unexplored. During the past decade or more, substantial progress has been made in developing antisense pharmacology. A great deal has been learned about the basic mechanisms of antisense, the medicinal chemistry, the pharmacological, pharmacokinetic and toxicological properties of antisense molecules. Antisense technology has proven of great value in gene functionalization and target validation. With one drug marketed, Vitravene, and approximately 20 antisense drugs in clinical development, it appears that antisense drugs may prove of value in the treatment of a wide range of diseases. In this review, the progress is summarized, the limitations of the technology discussed and the future considered.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Crooke STdoi
10.2174/1566524043360375keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
465-87issue
5eissn
1566-5240issn
1875-5666journal_volume
4pub_type
杂志文章,评审abstract::Until recently it was believed that TNF-induced apoptosis is mediated exclusively by TNF-RI because TNF-RII lacks death domain. However, it has been demonstrated that TNF-RII enhances TNF-RI-mediated apoptosis. In this review, I have discussed the evidence and mechanisms by which TNF-RII regulates TNF-alpha-induced ap...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013363780
更新日期:2001-07-01 00:00:00
abstract::Chemokines are newly discovered molecules that mediate the migration of leukocytes into inflammed tissues and control the inflammatory reactions in various immune-mediated diseases. Both in animal models and in human specimens, chemokine expression is associated with atherosclerotic lesion development and vascular rem...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033361546
更新日期:2003-03-01 00:00:00
abstract::Abnormal and prolonged inflammatory reaction is seen in a wide variety of disorders, and high level of Tumor Necrosis Factor alpha (TNF-α) has been linked to these disorders. Therefore, modulation of TNF-α expression is important in the regulation of inflammatory disorders. In our previous study, we have shown that a ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652411796268731
更新日期:2011-08-01 00:00:00
abstract::Transcutaneous immunization (TCI) involves the direct application of antigen plus adjuvant to skin, taking advantage of the large numbers of Langerhans cells and other resident skin dendritic cells, that process antigen then migrate to draining lymph nodes where immune responses are initiated. We have used this form o...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524054863906
更新日期:2005-09-01 00:00:00
abstract::Glutathione transferase Pi (GST-pi, GSTP) is known to strongly affect human susceptibility to several cancers, asthma and neurodegenerative disorders. As with other glutathione transferases, it catalyses the addition of reduced glutathione to electrophilic species, and it is important in metabolite detoxification. It ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411794859278
更新日期:2011-03-01 00:00:00
abstract::Germline mutations in the VHL tumour suppressor gene may cause a variety of phenotypes including von Hippel-Lindau (VHL) disease, familial phaeochromocytoma and inherited polycythaemia. VHL disease is a multisystem familial cancer syndrome and is the commonest cause of familial renal cell carcinoma (RCC). VHL disease ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043359827
更新日期:2004-12-01 00:00:00
abstract::Peroxisomal proliferator activated receptor gamma (PPARgamma) belongs to the family of nuclear hormone receptors (NHRs), which directly regulate transcription of target genes. The regulatory role of this receptor on lipid metabolism and insulin sensitization is well established. Recently, the overexpression of this re...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407781695765
更新日期:2007-09-01 00:00:00
abstract::Mood disorders and schizophrenia share a number of common properties, including: genetic susceptibility; differences in brain structure and drug based therapy. Some genetic loci may even confer susceptibility for bipolar mood disorder and schizophrenia, and some atypical antipsychotic drugs are used as mood stabilizer...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479672
更新日期:2003-08-01 00:00:00
abstract::In this study, a two-dimensional gel-based proteomic approach was applied to profile the protein alterations underlying the significant adverse effects from post-stroke depression (PSD). In view of the close association between left prefrontal cortical dysfunction and PSD, a PSD rat model was constructed through a lef...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666141021143333
更新日期:2014-01-01 00:00:00
abstract::Carcinoma-associated fibroblasts (CAFs) are activated fibroblasts during development of several cancer types, and therefore emerge as an attractive therapeutic target for cancer therapy. Drugs such as PT-100 and sibrotuzumab that block the functions of CAFs have already been in clinical trials. However, these drugs ex...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524018666171205113959
更新日期:2017-01-01 00:00:00
abstract:PURPOSE:A small molecular compound, aminooxy-acetic acid (AOA), has been shown to modulate experimental autoimmune encephalomyelitis (EAE). The current study was designed to investigate whether AOA has a similar effect on the development of experimental autoimmune uveitis (EAU) and to further explore underlying mechani...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200211112219
更新日期:2020-01-01 00:00:00
abstract::Nitric oxide has emerged as one of the most important and diverse players in physiology. This small diatomic radical stunned researchers because of its existence and unique biological properties in human physiology. Over the last two decades it was found that NO often has fickle behavior in pathophysiological mechanis...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043359854
更新日期:2004-11-01 00:00:00
abstract::Glycogen is a branched polymer of glucose which serves as a reservoir of glucose units. The two largest deposits in mammals are in the liver and skeletal muscle but many cells are capable synthesizing glycogen. Its accumulation and utilization are under elaborate controls involving primarily covalent phosphorylation a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524024605761
更新日期:2002-03-01 00:00:00
abstract:PURPOSE:Accumulated evidence have well established that protein sumoylation plays multiple roles in various cellular processes. In the vertebrate eye, we and others have demonstrated that sumoylation displays indispensable roles in regulating eye development. Various ocular cell lines including human embryonic cell lin...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190107153440
更新日期:2018-01-01 00:00:00
abstract::Prolylcarboxypeptidase isoform 1 (PRCP1) is capable of regulating numerous autocrines and hormones, such as angiotensin II, angiotensin III, αMSH1-13, and DesArg(9) bradykinin. It does so by cleaving a C-terminal PRO-X bond. Recent work also indicates that the human PRCP1 activates plasma prekallikrein (PK) to kallikr...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666141015153519
更新日期:2014-01-01 00:00:00
abstract::Gastric cancer is thought to result from a combination of environmental factors and the accumulation of specific genetic alterations due to increasing genetic instability, and consequently affects mainly older patients. Less than 10% of patients present with the disease before 45 years of age (early onset gastric carc...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407779940503
更新日期:2007-02-01 00:00:00
abstract::Extracellular matrices (ECMs) are dynamic structures that provide cells not only with a structural support but, importantly, exhibit significant functional roles in the control of key cellular events such as adhesion, migration, proliferation, differentiation, and survival. In tumors, matrix effectors such as proteogl...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412802480943
更新日期:2012-09-01 00:00:00
abstract::Endometriosis is one of the most common gynecological inflammatory diseases, occurring in adolescents and women in the reproductive age group and leading to infertility. The precise etiopathogenesis of endometriosis is unknown, but several theories concerning the phenomena involved in its development have been propose...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666150921105218
更新日期:2015-01-01 00:00:00
abstract::Preeclampsia is a disease of high incidence in pregnant women which complicates pregnancy and may lead to the death of mother and baby. Preeclampsia is characterized by a series of clinical features such as hypertension and proteinuria associated with endothelial dysfunction. Although the causes of disease have not be...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/15665240113139990058
更新日期:2013-09-01 00:00:00
abstract::The world is aging and we must face the challenges that this brings. One of the reasons for the increasing aging of the world's population is the increase in life expectancy and, since we live longer, it is of paramount importance to live well and to prevent age-associated diseases. In this way, it is crucial to impro...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524018666180907162955
更新日期:2018-01-01 00:00:00
abstract::By eliminating the unneeded or mutant cells, programmed cell death actively participates in a wide range of biological processes from embryonic development to homeostasis maintenance in adult. Continuing efforts have identified multiple cell death pathways, with apoptosis, necrosis and autophage the mostly studied. Re...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666151026100339
更新日期:2015-01-01 00:00:00
abstract::Type 2 diabetes (T2D) is a metabolic disorder characterised by the inability of β-cells to secrete enough insulin to maintain glucose homeostasis. Pancreatic β-cells secrete insulin in a biphasic manner, first and second phase insulin secretion, and loss of first phase insulin secretion is an independent predictor of ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts a cancer cell-specific pro-apoptotic activity. This property made the TRAIL associated pathway one of the most promising strategies aimed at inducing tumor-selective death. In fact, several approaches have been considered to explore this pathwa...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652413804810727
更新日期:2013-02-01 00:00:00
abstract::PTEN (Phosphatase and Tensin homologue deleted on chromosome 10, 10q23.3) is the dominant phosphatase responsible for the dephosphorylation of the 3-position phosphate from the inositol ring of phosphatidylinositol 3,4,5 triphosphate (PIP3), and thereby directly antagonizes the actions mediated by Phosphatidylinositol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013666131118100542
更新日期:2014-01-01 00:00:00
abstract::Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408783565595
更新日期:2008-02-01 00:00:00
abstract::Cholesterol is a chameleon bio-molecule in cellular multiplex. It acts as a prelate in almost every cellular compartment with its site specific characteristics viz. regulation of structural veracity and scaffold fluidity of bio-membranes, insulation of electrical transmission in nerves, controlling of genes by making ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200413112030
更新日期:2020-01-01 00:00:00
abstract::Charcot-Marie-Tooth disease (CMT) and related neuropathies are a genetically highly heterogeneous group of neurodegenerative disorders. CMT affects both the sensory and motor nerves, distal Hereditary Motor Neuropathies (dHMN) are phenotypically similar disorders involving only motor nerves, while Hereditary Sensory a...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666141010154205
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Obesity is a chronic condition associated with poorer cognitive functioning. Wisconsin Card Sorting Test (WCST) is a useful tool for evaluating executive functions. In this study, we assessed the association between dopaminergic gene polymorphisms: DAT1 (SLC6A3), COMTVal158Met, DRD4 (48-bp variable number of...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190424143653
更新日期:2019-01-01 00:00:00
abstract::Many autoimmune diseases have genetic associations with the Major Histocompatibility Complex (MHC) class II loci. Susceptibility to Type 1 diabetes mellitus (TIDM) is particularly associated with Human Leucocyte Antigen (HLA) DR3, 4 and associated DQ2, 8 alleles and this is well documented in genetic association studi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033361591
更新日期:2003-02-01 00:00:00
abstract::Skin is a complex tissue composed of two very different compartments -- the continuously renewing epidermis made up mostly by keratinocytes and the underlying matrix-rich dermis with the resting fibroblasts as its major cellular components. Both compartments are tightly interconnected and a paracrine mutual interactio...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524053586644
更新日期:2005-03-01 00:00:00