Main description:

This volume provides a concise and technical discussion of recently developed approaches to overcome challenges, such as pharmacodynamics and pharmacokinetics difficulties, in miRNA drug discovery. These strategies cover anti-sense agents targeting miRNA that are applied in advanced formulations or are chemically optimized to increase delivery; small molecule miRNA modulators to overcome anti-sense agents' limitations; general enhancers of miRNA maturation; and Argonaute 2 protein and its pharmacokinetic parameters. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.

Cutting-edge and thorough, Drug Target miRNA: Methods and Protocols is a valuable resource for anyone interested in the ever-evolving field of miRNA drug discovery.

Contents:

PART I Reviews

1. MiRNA Targeting Drugs: The Next Blockbusters?
Marco F. Schmidt

PART II Protocols

2. Functional Analysis of miRNA using DIANA Tools Online Suite
Ionnis S. Vlachos and Artemis G. Hatzigeorgiou

3. Non-Nucleotide Modification of Anti-miRNA Oligonucleotides
Kim A. Lennox, Christopher A. Vakulskas, and Mark A. Behlke

4. Quantification of Oligonucleotide Association with miRNA-Argonaute Complexes In Vitro
Dimitrios G. Zisoulis

5. Determination of Anti-miR Association with miRNA/Argonaute Complexes In Vivo
Dimitrios G. Zisoulis
6. Competitive Argonaute-Based RNA Immunoprecipitation for Investigation of Transcriptomic Response to Anti-miR
John R. Androsavich
7. Assessing Anti-miR Pharmacology with miRNA Polysome Shift Assay
John R. Androsavich

8. Evaluating Synergistic Effects of miR-34a Mimics in Combination with Other Therapeutic Agents in Cultured Non-Small Cell Lung Cancer Cells
Jane Zhao and Andreas G. Bader
9. Assessing the Off-Target Effects of miRNA Inhibitors on Innate Immune Toll-Like Receptors
Genevieve Pepin, Jonathan Ferrand, and Michael P. Gantier
10. Design of Multimodal Small Molecules Targeting miRNA Biogenesis: Synthesis and In Vitro Evaluation
Duc D. Vo and Maria Duca
11. Machine Learning Approaches towards Building Predictive Models for Small Molecule Modulators of miRNA and its Utility in Virtual Screening of Molecular Databases
Vinita Periwal and Vinod Scaria
12. Identification of Small Molecule Modulators of MicroRNA by Library Screening
Yangchao Chen
13. Rapid Generation of miRNA Inhibitor Leads by Bio-Informatics and Efficient High-Throughput Screening Methods
Christopher L. Haga, Sai Pradeep Velagapudi, Jessica L. Childs-Disney, Jacqueline Strivelli, Matthew D. Disney, and Donald G. Phinney
14. Peptide-Based Inhibition of miRNA-Guided Gene Silencing
Johannes Danner, Balagopal Pai, Ludwig Wankerl, and Gunter Meister
15. Small Molecules Targeting the miRNA Binding Domain of Argonaute 2: From Computer-Aided Molecular Design to RNA Immunoprecipitation
Teresa Bellissimo, Silvia Masciarelli, Elena Poser, Ilaria Genovese, Alberto Del Rio, Gianni Colotti, and Francesco Fazi

16. Surface Plasmon Resonance: A Useful Strategy for the Identification of Small Molecule Argonaute 2 Protein Binders
Elena Poser, Ilaria Genovese, Silvia Masciarelli, Teresa Bellisimo, Francesco Fazi, and Gianni Colotti
17. Antagonists of the miRNA-Argonaute 2 Protein Complex: Anti-miR-AGOs
Marco F. Schmidt, Oliver Korb, and Chris Abell
18. Elucidating Mechanisms of Molecular Recognition between Human Argonaute and miRNA using Computational ApproachesHanlun Jiang, Lizhe Zhu, Amelie Heliou, Xin Gao, Julie Bernbauer, and Xuhui Huang
19. Kinetic Analysis of Target RNA Binding and Slicing by Argonaute 2 Protein
Sarah Willkomm and Tobias Restle
20. Site-Specific Fluorescent Labeling of Argonaute for FRET-Based Bio-Assays
Sarah Willkomm, Adrian Zander, and Diana Grohmann
21. Single-Molecule Fluorescence Energy Transfer Assays for the Characterization of Reaction Pathways of miRNA-Argonaute Complex
Myung Hyun Jo and Sungchul Hohng