Abstract
The discovery of RNA interference (RNAi) in eukaryotic cells has been the major recent breakthrough in molecular and cell biology. RNAi machineries exert biological functions in gene regulation, genome defense and chromatin architecture and dynamics. The potential of RNAi to silence any gene of interest in a highly specific and efficient manner via double-stranded RNA (dsRNA) has literally revolutionized modern genetics. RNAi-based functional genomics now permits, for the first time, to evaluate the cellular role of individual gene products on a genome-wide scale in higher organisms like mammals, presenting an alternative to the generation of animal knockouts often doomed to failure because of a lethal phenotype. RNAi has had an enormous impact on the development of novel disease models in animals, and it is likely that small interfering RNAs (siRNAs), which are the trigger molecules for RNA silencing, will become an invaluable tool for the treatment of genetic diseases. First clinical trials, using siRNAs directed against the vascular endothelial growth factor (VEGF) or one of its receptors, have been initiated recently for the treatment of age-related macular degeneration. Improving guidelines for the rational design of siRNAs, based on recent progress in understanding the mechanisms underlying RNAi, as well as the introduction of chemical modifications into siRNAs are expected to improve their pharmacokinetic and pharmacodynamic properties for in vivo applications. Finally, successful therapeutic application of RNAi will depend on the development of improved siRNA delivery strategies that combine high specificity and efficiency with a low immunostimulatory and tumorigenic potential.
Keywords: RNA interference, RNAi, RNA silencing, siRNA, miRNA, shRNA, RISC, therapeutic application
Current Medicinal Chemistry
Title: RNA Interference as A Gene-Specific Approach for Molecular Medicine
Volume: 12 Issue: 26
Author(s): A. Grunweller and R. K. Hartmann
Affiliation:
Keywords: RNA interference, RNAi, RNA silencing, siRNA, miRNA, shRNA, RISC, therapeutic application
Abstract: The discovery of RNA interference (RNAi) in eukaryotic cells has been the major recent breakthrough in molecular and cell biology. RNAi machineries exert biological functions in gene regulation, genome defense and chromatin architecture and dynamics. The potential of RNAi to silence any gene of interest in a highly specific and efficient manner via double-stranded RNA (dsRNA) has literally revolutionized modern genetics. RNAi-based functional genomics now permits, for the first time, to evaluate the cellular role of individual gene products on a genome-wide scale in higher organisms like mammals, presenting an alternative to the generation of animal knockouts often doomed to failure because of a lethal phenotype. RNAi has had an enormous impact on the development of novel disease models in animals, and it is likely that small interfering RNAs (siRNAs), which are the trigger molecules for RNA silencing, will become an invaluable tool for the treatment of genetic diseases. First clinical trials, using siRNAs directed against the vascular endothelial growth factor (VEGF) or one of its receptors, have been initiated recently for the treatment of age-related macular degeneration. Improving guidelines for the rational design of siRNAs, based on recent progress in understanding the mechanisms underlying RNAi, as well as the introduction of chemical modifications into siRNAs are expected to improve their pharmacokinetic and pharmacodynamic properties for in vivo applications. Finally, successful therapeutic application of RNAi will depend on the development of improved siRNA delivery strategies that combine high specificity and efficiency with a low immunostimulatory and tumorigenic potential.
Export Options
About this article
Cite this article as:
Grunweller A. and Hartmann K. R., RNA Interference as A Gene-Specific Approach for Molecular Medicine, Current Medicinal Chemistry 2005; 12 (26) . https://dx.doi.org/10.2174/092986705774933489
DOI https://dx.doi.org/10.2174/092986705774933489 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Whole Cell Biocatalysts for the Preparation of Nucleosides and their Derivatives
Current Pharmaceutical Design Driving Neural Stem Cells Towards a Desired Phenotype
Current Stem Cell Research & Therapy When Neighbors Talk: Colon Cancer Cell Invasion and Tumor Microenvironment Myofibroblasts
Current Drug Targets Synthesis and Evaluation of 2-Substituted Fendiline Analogues as Antileukemics
Letters in Drug Design & Discovery Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation
Current Pharmaceutical Design Understanding Autophagy in Cell Death Control
Current Pharmaceutical Design Merkel Cell Carcinoma: Epidemiology, Clinical Presentations, Histology, Polyomavirus Involvement, and Management
Current Cancer Therapy Reviews Real-Time PCR: Revolutionizing Detection and Expression Analysis of Genes
Current Genomics Targeting Glioblastoma Stem Cells: Cell Surface Markers
Current Medicinal Chemistry Determination of 7,12-Dimethylbenz[a]Anthracene in Orally Treated Rats by High-Performance Liquid Chromatography and Transfer Stripping Voltammetry
Combinatorial Chemistry & High Throughput Screening Emerging Roles of MicroRNA-22 in Human Disease and Normal Physiology
Current Molecular Medicine Altered Glycosylation of Proteins in Cancer: What Is the Potential for New Anti-Tumour Strategies
Anti-Cancer Agents in Medicinal Chemistry Base-Modified Nucleosides as Chemotherapeutic Agents: Past and Future
Current Topics in Medicinal Chemistry Development of Patents and Clinical Trials on Regenerative Therapy: Gene Therapy
Recent Patents on Regenerative Medicine Bortezomib as the First Proteasome Inhibitor Anticancer Drug: Current Status and Future Perspectives
Current Cancer Drug Targets Immunosuppressive Therapy for Myelodysplastic Syndromes
Current Pharmaceutical Design Exploring Mechanisms of MicroRNA Downregulation in Cancer
MicroRNA Chemical Metabolic Inhibitors for the Treatment of Blood-Borne Cancers
Anti-Cancer Agents in Medicinal Chemistry Phytochemical-Mediated Glioma Targeted Treatment: Drug Resistance and Novel Delivery Systems
Current Medicinal Chemistry Regulatory Approaches to Nonclinical Reproductive Toxicity Testing of Anti-Cancer Drugs
Anti-Cancer Agents in Medicinal Chemistry