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
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...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
- 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
-
Double Point Modified Analogs of Vitamin D as Potent Activators of Vitamin D Receptor
Current Pharmaceutical Design Estrogen Receptor Alpha: Impact of Ligands on Intracellular Shuttling and Turnover Rate in Breast Cancer Cells
Current Cancer Drug Targets Tyrosine Kinase Inhibitors – A Review on Pharmacology, Metabolism and Side Effects
Current Drug Metabolism NK-1 Receptor Antagonists: A New Paradigm in Pharmacological Therapy
Current Medicinal Chemistry Probing into Therapeutic Anti-cancer Potential of Apigenin: Recent Trends and Future Directions
Recent Patents on Inflammation & Allergy Drug Discovery α2-Adrenoceptors Enhance Cell Proliferation and Mammary Tumor Growth Acting Through both the Stroma and the Tumor Cells
Current Cancer Drug Targets Surgical Management of Medullary Thyroid Carcinoma in Pediatric Age
Current Pediatric Reviews Is There a Role for Antioxidants in the Prevention of Infection-Associated Carcinogenesis and in the Treatment of Infection-Driven Tumors?
Current Topics in Medicinal Chemistry Development of Prodrugs for Enzyme-Mediated, Tumor-Selective Therapy
Current Medicinal Chemistry - Anti-Cancer Agents SALL4: Engine of Cell Stemness
Current Gene Therapy Structural and Functional Characterization of the Proteins Responsible for N<sup>6</sup>-Methyladenosine Modification and Recognition
Current Protein & Peptide Science Pre-Clinical and Clinical Evaluation of Nuclear Tracers for the Molecular Imaging of Vulnerable Atherosclerosis: An Overview
Current Medicinal Chemistry Immunotherapy and Cancer Vaccines in the Management of Breast Cancer
Current Pharmaceutical Design Thioredoxin Reductase and its Inhibitors
Current Protein & Peptide Science Exploring Promises of siRNA in Cancer Therapeutics
Current Cancer Therapy Reviews Radiolabeled Peptide Probes for Liver Cancer Imaging
Current Medicinal Chemistry Epigenetic Changes Induced by Green Tea Catechins a re Associated with Prostate Cancer
Current Molecular Medicine Flexible Bronchoscopy: Importance of Standardization of Practice for the Best Route of Insertion.
Current Respiratory Medicine Reviews Novel Inhibitors of DNA Repair Enzyme TDP1 Combining Monoterpenoid and Adamantane Fragments
Anti-Cancer Agents in Medicinal Chemistry The Putative Use of Lithium in Alzheimer’s Disease
Current Alzheimer Research