Abstract
High throughput technologies have the potential to affect all aspects of drug discovery. Considerable attention is paid to high throughput screening (HTS) for small molecule lead compounds. The identification of the targets that enter those HTS campaigns had been driven by basic research until the advent of genomics level data acquisition such as sequencing and gene expression microarrays. Large-scale profiling approaches (e.g., microarrays, protein analysis by mass spectrometry, and metabolite profiling) can yield vast quantities of data and important information. However, these approaches usually require painstaking in silico analysis and low-throughput basic wet-lab research to identify the function of a gene and validate the gene product as a potential therapeutic drug target. Functional genomic screening offers the promise of direct identification of genes involved in phenotypes of interest. In this review, RNA interference (RNAi) mediated loss-of-function screens will be discussed and as well as their utility in target identification. Some of the genes identified in these screens should produce similar phenotypes if their gene products are antagonized with drugs. With a carefully chosen phenotype, an understanding of the biology of RNAi and appreciation of the limitations of RNAi screening, there is great potential for the discovery of new drug targets.
Combinatorial Chemistry & High Throughput Screening
Title: Discovery of Novel Targets with High Throughput RNA Interference Screening
Volume: 11 Issue: 3
Author(s): Paul D. Kassner*
Affiliation:
- Lead Discovery Department,Amgen Inc., ASF1-2118, 1120 Veterans Blvd., South San Francisco, CA 94080, USA.,United States
Abstract: High throughput technologies have the potential to affect all aspects of drug discovery. Considerable attention is paid to high throughput screening (HTS) for small molecule lead compounds. The identification of the targets that enter those HTS campaigns had been driven by basic research until the advent of genomics level data acquisition such as sequencing and gene expression microarrays. Large-scale profiling approaches (e.g., microarrays, protein analysis by mass spectrometry, and metabolite profiling) can yield vast quantities of data and important information. However, these approaches usually require painstaking in silico analysis and low-throughput basic wet-lab research to identify the function of a gene and validate the gene product as a potential therapeutic drug target. Functional genomic screening offers the promise of direct identification of genes involved in phenotypes of interest. In this review, RNA interference (RNAi) mediated loss-of-function screens will be discussed and as well as their utility in target identification. Some of the genes identified in these screens should produce similar phenotypes if their gene products are antagonized with drugs. With a carefully chosen phenotype, an understanding of the biology of RNAi and appreciation of the limitations of RNAi screening, there is great potential for the discovery of new drug targets.
Export Options
About this article
Cite this article as:
Kassner D. Paul*, Discovery of Novel Targets with High Throughput RNA Interference Screening, Combinatorial Chemistry & High Throughput Screening 2008; 11 (3) . https://dx.doi.org/10.2174/138620708783877744
DOI https://dx.doi.org/10.2174/138620708783877744 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...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
-
Montelukast Efficacy for Improvement of Adult Acute Phase Mild-Moderate Asthma Attack: A Clinical Trial Study
Current Respiratory Medicine Reviews Toll-Like Receptors and their Role in Renal Pathologies
Inflammation & Allergy - Drug Targets (Discontinued) Peroxisome Proliferator-Activated Receptor-γ in Vascular Biology
Cardiovascular & Hematological Disorders-Drug Targets The Emergence of Immune-checkpoint Inhibitors in Colorectal Cancer Therapy
Current Drug Targets Statins: Are They All the Same?
Current Drug Therapy Cannabinoids and Neuroprotection in Motor-Related Disorders
CNS & Neurological Disorders - Drug Targets Pharmaceutical Treatment of Asthma in Children
Current Drug Targets - Inflammation & Allergy The Transcriptional Regulation of the Human CYP2C Genes
Current Drug Metabolism Cyclooxygenase-2 Inhibitors: A Painful Lesson
Cardiovascular & Hematological Disorders-Drug Targets Anti Inflammatory and Anti Arthritic Activity of Different Milk Based Formulation of Curcumin in Rat Model
Current Drug Delivery Prediction of Degeneration of Native and Bioprosthetic Aortic Valves:Issue-Related Particularities of Diabetes Mellitus
Infectious Disorders - Drug Targets Combined Treatment with PPAR-γ Agonists in Pancreatic Cancer: A Glimmer of Hope for Cancer Therapy?
Current Cancer Drug Targets Targeting the mTOR Pathway in Tumor Malignancy
Current Cancer Drug Targets Antihypertensive Drugs Metabolism: An Update to Pharmacokinetic Profiles and Computational Approaches
Current Pharmaceutical Design Alcohol Use Disorder and Dementia: Critical Mechanisms for Cognitive Loss
Current Neurovascular Research Non-Invasive Cell Tracking in Cancer and Cancer Therapy
Current Topics in Medicinal Chemistry Inducible Nitric Oxide Synthase Inhibition by Mycophenolic Acid
Mini-Reviews in Medicinal Chemistry MicroRNAs and Cancer Therapy – From Bystanders to Major Players
Current Medicinal Chemistry Nutritional and Therapeutic Potential of Garlic and Onion (Allium sp.)
Current Nutrition & Food Science Simultaneous multicolor luciferase reporter assays for monitoring of multiple genes expressions
Combinatorial Chemistry & High Throughput Screening