Abstract
Antisense technology, which is based on a simple and rational principle of Watson-Crick complementary base pairing of a short oligonucleotide with the targeted mRNA to downregulate the diseasecausing gene product, has progressed tremendously in the last two decades. Antisense oligonucleotides targeted to a number of cancer-causing genes are being evaluated in human clinical trials. While the firstgeneration phosphorothioate antisense oligonucleotides are in clinical trials, a number of factors, including sequence motifs that could lead to unwanted mechanisms of action and side effects, have been identified. The severity of the side effects of first-generation antisense oligonucleotides is mostly dependent on the presence of certain sequence motifs, such as CpG dinucleotides. A number of second-generation chemical modifications have been proposed to overcome the limitations of the first-generation antisense oligonucleotides. The safety and efficacy of several second-generation mixed-backbone antisense oligonucleotides are being evaluated in clinical trials. The immune stimulation affects observed with CpG-containing antisense oligonucleotides are being exploited as a novel therapeutic modality, with several CpG oligonucleotides being evaluated in clinical trials. A number of medicinal chemistry studies performed to date suggest that the immunomodulatory activity of CpG oligonucleotides can be fine-tuned by site-specific incorporation of chemical modifications in order to design disease-specific oligonucleotide therapeutics.
Current Cancer Drug Targets
Title: Antisense and/or Immunostimulatory Oligonucleotide Therapeutics
Volume: 1 Issue: 3
Author(s): Sudhir Agrawal and Ekambar R. Kandimalla
Affiliation:
Abstract: Antisense technology, which is based on a simple and rational principle of Watson-Crick complementary base pairing of a short oligonucleotide with the targeted mRNA to downregulate the diseasecausing gene product, has progressed tremendously in the last two decades. Antisense oligonucleotides targeted to a number of cancer-causing genes are being evaluated in human clinical trials. While the firstgeneration phosphorothioate antisense oligonucleotides are in clinical trials, a number of factors, including sequence motifs that could lead to unwanted mechanisms of action and side effects, have been identified. The severity of the side effects of first-generation antisense oligonucleotides is mostly dependent on the presence of certain sequence motifs, such as CpG dinucleotides. A number of second-generation chemical modifications have been proposed to overcome the limitations of the first-generation antisense oligonucleotides. The safety and efficacy of several second-generation mixed-backbone antisense oligonucleotides are being evaluated in clinical trials. The immune stimulation affects observed with CpG-containing antisense oligonucleotides are being exploited as a novel therapeutic modality, with several CpG oligonucleotides being evaluated in clinical trials. A number of medicinal chemistry studies performed to date suggest that the immunomodulatory activity of CpG oligonucleotides can be fine-tuned by site-specific incorporation of chemical modifications in order to design disease-specific oligonucleotide therapeutics.
Export Options
About this article
Cite this article as:
Sudhir Agrawal and Ekambar R. Kandimalla , Antisense and/or Immunostimulatory Oligonucleotide Therapeutics, Current Cancer Drug Targets 2001; 1 (3) . https://dx.doi.org/10.2174/1568009013334160
DOI https://dx.doi.org/10.2174/1568009013334160 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
Unraveling the Tumor Microenvironment and Potential Therapeutic Targets: Insights from Single-Cell Sequencing and Spatial Transcriptomics
This special issue will focus on unraveling the complexities of the tumor microenvironment (TME) and identifying key biomarkers for potential therapeutic targets using advanced multi-omics techniques, such as single-cell sequencing and spatial transcriptomics. We seek original research and comprehensive reviews that investigate the heterogeneity and dynamics of the TME, emphasizing ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Role of Chemotherapy and Radiation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
Current Drug Targets DNA Demethylation: Where Genetics Meets Epigenetics
Current Pharmaceutical Design In Silico Identification of Human miR 3654 and its Targets Revealed its Involvement in Prostate Cancer Progression
MicroRNA Genetic Molecular Subtypes in Optimizing Personalized Therapy for Metastatic Colorectal Cancer
Current Drug Targets Targeting Cell Death and Survival Receptors in Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member
Anti-Cancer Agents in Medicinal Chemistry Protein Engineering: A New Frontier for Biological Therapeutics
Current Drug Metabolism Exploiting APC Function as a Novel Cancer Therapy
Current Drug Targets Engineering of Plant Metabolism for Drug and Food
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Synthesis and Preliminary Biological Evaluation of Polyamine-aniline Acridines as P-glycoprotein Inhibitors
Medicinal Chemistry Applications of Nuclear Technique to Biological Sciences Labelled Compounds, Radioactive Tracers, and X-Ray Tomography
Current Topics in Medicinal Chemistry Endothelial Progenitor Cells as Potential Drug Targets
Current Drug Targets - Cardiovascular & Hematological Disorders Discovery of Small Molecule c-Met Inhibitors: Evolution and Profiles of Clinical Candidates
Anti-Cancer Agents in Medicinal Chemistry Editorial
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Small Airways Disease in Asthma
Current Respiratory Medicine Reviews A Mini-review on HER2 Positive Breast Cancer and its Metastasis: Resistance and Treatment Strategies
Current Nanomedicine Potential Role of Biological Systems in Formation of Nanoparticles: Mechanism of Synthesis and Biomedical Applications
Current Nanoscience The Histone Deacetylase Inhibitor, MS-275 (Entinostat), Downregulates c-FLIP, Sensitizes Osteosarcoma Cells to FasL, and Induces the Regression of Osteosarcoma Lung Metastases
Current Cancer Drug Targets Radiation and Gene Therapy: Rays of Hope for the New Millennium?
Current Gene Therapy Drug Discovery Using Yeast as a Model System: A Functional Genomic and Proteomic View
Current Proteomics