Abstract
Currently rational drug design is limited to using protein targets in the design and production of therapeutic agents. However, many genetic and infectious diseases may not be adequately treated with this approach. In these circumstances the DNA sequence of an offending gene is itself a potential target for rational drug development. Genetargeted therapeutic strategies require the development of ligands that can recognize and bind unique DNA targets sequence specifically. Several approaches have been described for the development of sequence-specific DNA targeting agents. These include synthetic polyamides that recognize and bind to DNA in the minor groove, peptide nucleic acids which can penetrate the DNA duplex and form a P-loop, or a triple-helical structure with one of its strands, and triplehelix (triplex) forming oligonucleotides which bind to the major groove of duplex DNA at polypyrimidine / polypurine sequences. Of these, Triplex-Forming Oligonucleotides (TFOs) are the most extensively characterized synthetic ligands capable of recognizing and binding sequence specifically to duplex DNA. Consequently, they have been the focus of a new gene therapy strategy that we call ‘anti-gene radiotherapy’. This strategy employs TFOs labeled with Auger-electronemitting radionuclides to produce sequence-specific DNA double strand breaks that ultimately lead to gene inactivation following repair. Anti-gene radiotherapy is made possible by the highly localized damage produced by decay of an Augeremitter, such as 125I, and the sequence specific positioning of DNA damage made possible by TFOs. This report will address recently described strategies that employ these gene-targeting methods to alter target gene expression or structure, with particular emphasis being paid to the use of TFOs in anti-gene radiotherapy.
Keywords: gene-targeted agents, anti-gene radio therapy, triplex-forming oligonucleotide, tfos
Current Genomics
Title: Rational Drug Development Using Gene-Targeted Agents and Their Application in Anti-Gene Radiotherapy
Volume: 4 Issue: 3
Author(s): Thomas A. Winters, Elzbieta Pastwa, Kamal Datta and Ronald D. Neumann
Affiliation:
Keywords: gene-targeted agents, anti-gene radio therapy, triplex-forming oligonucleotide, tfos
Abstract: Currently rational drug design is limited to using protein targets in the design and production of therapeutic agents. However, many genetic and infectious diseases may not be adequately treated with this approach. In these circumstances the DNA sequence of an offending gene is itself a potential target for rational drug development. Genetargeted therapeutic strategies require the development of ligands that can recognize and bind unique DNA targets sequence specifically. Several approaches have been described for the development of sequence-specific DNA targeting agents. These include synthetic polyamides that recognize and bind to DNA in the minor groove, peptide nucleic acids which can penetrate the DNA duplex and form a P-loop, or a triple-helical structure with one of its strands, and triplehelix (triplex) forming oligonucleotides which bind to the major groove of duplex DNA at polypyrimidine / polypurine sequences. Of these, Triplex-Forming Oligonucleotides (TFOs) are the most extensively characterized synthetic ligands capable of recognizing and binding sequence specifically to duplex DNA. Consequently, they have been the focus of a new gene therapy strategy that we call ‘anti-gene radiotherapy’. This strategy employs TFOs labeled with Auger-electronemitting radionuclides to produce sequence-specific DNA double strand breaks that ultimately lead to gene inactivation following repair. Anti-gene radiotherapy is made possible by the highly localized damage produced by decay of an Augeremitter, such as 125I, and the sequence specific positioning of DNA damage made possible by TFOs. This report will address recently described strategies that employ these gene-targeting methods to alter target gene expression or structure, with particular emphasis being paid to the use of TFOs in anti-gene radiotherapy.
Export Options
About this article
Cite this article as:
Winters A. Thomas, Pastwa Elzbieta, Datta Kamal and Neumann D. Ronald, Rational Drug Development Using Gene-Targeted Agents and Their Application in Anti-Gene Radiotherapy, Current Genomics 2003; 4 (3) . https://dx.doi.org/10.2174/1389202033490420
DOI https://dx.doi.org/10.2174/1389202033490420 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Related Journals
- 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
- Announcements
Related Articles
-
Dysregulation of LncRNAs in Placenta and Pathogenesis of Preeclampsia
Current Drug Targets The Link Between Conventional and Novel Anti-Cancer Therapeutics with Thrombotic Microangiopathy
Drug Metabolism Letters Intravesical Drug Delivery into the Bladder to Treat Cancers
Current Drug Delivery Drug Targets to Pro-Angiogenetic Factors with Special Reference to Primary Peritoneal Mesothelioma
Endocrine, Metabolic & Immune Disorders - Drug Targets Using Pharmacologic Data to Plan Clinical Treatments for Patients with Peritoneal Surface Malignancy
Current Drug Discovery Technologies Mechanism of Cancer Drug Resistance and the Involvement of Noncoding RNAs
Current Medicinal Chemistry Review on Documented Medicinal Plants used for the Treatment of Cancer
Current Traditional Medicine Advances in Clinical Study of Curcumin
Current Pharmaceutical Design Nanoparticle Albumin - Bound (NAB) Technology is a Promising Method for Anti-Cancer Drug Delivery
Recent Patents on Anti-Cancer Drug Discovery Subject Index To Volume 6
Current Topics in Medicinal Chemistry Metastasis: Recent Discoveries and Novel Perioperative Treatment Strategies with Particular Interest in the Hemostatic Compound Desmopressin
Current Pharmaceutical Biotechnology Future Prospect of RNA Interference for Cancer Therapies
Current Drug Targets COX-2 Selective Inhibitors, Carbonic Anhydrase Inhibition and Anticancer Properties of Sulfonamides Belonging to This Class of Pharmacological Agents
Mini-Reviews in Medicinal Chemistry Kruppel-Like Factors 4 and 5: Unity in Diversity
Current Genomics Meet Our Editorial Board Member
Current Medicinal Chemistry Coupling of Conjugating Enzymes and Efflux Transporters: Impact on Bioavailability and Drug Interactions
Current Drug Metabolism Gene Silencing in the Development of Personalized Cancer Treatment: The Targets, the Agents and the Delivery Systems
Current Gene Therapy Clinical Development of MET Targeted Therapy For Human Cancer
Current Cancer Therapy Reviews Potential Molecular Targeted Therapeutics: Role of PI3-K/Akt/mTOR Inhibition in Cancer
Anti-Cancer Agents in Medicinal Chemistry The Use of the Zebrafish Model to Aid in Drug Discovery and Target Validation
Current Topics in Medicinal Chemistry