Download or read book New Advances in RNA Targeting written by Olga N. Ilinskaya and published by Frontiers Media SA. This book was released on 2020-06-04 with total page 251 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book RNA as a Drug Target written by John Schneekloth and published by John Wiley & Sons. This book was released on 2024-10-07 with total page 418 pages. Available in PDF, EPUB and Kindle. Book excerpt: Discover a new paradigm in drug discovery that greatly expands the space of addressable drug targets and potential novel drugs Existing paradigms for drug discovery have focused largely on enzymes and other proteins as drug targets. In recent years, however, different varieties of ribonucleic acids have emerged as a viable focus for target-based drug discovery, with the potential to revolutionize the strategy and approach for this essential step in the drug development process. RNA as a Drug Target: The Next Frontier for Medicinal Chemistry offers a practice-oriented introduction to developing drug-like small molecules that selectively modulate both coding and non-coding RNAs. Beginning with a description and characterization of existing druggable RNAs, the book discusses how to approach different RNA targets for drug discovery. The result is a crucial resource for targeting RNAs and creating the next generation of life-saving pharmaceuticals. RNA as a Drug Target readers will also find: A complete “toolbox” for working with RNA, from structure determination to screening and lead generation techniques A wide range of addressable targets and mechanisms, including splicing modulation, riboswitches, targeted degradation, and more Authoritative discussion of the potential of RNA-targeted small molecule therapeutics for drugging the epitranscriptome RNA as a Drug Target provides an expert introduction to a new frontier in pharmaceutical research for medicinal chemists, biochemists, molecular biologists, and members of the pharmaceutical industry.
Download or read book Long Non Coding RNA Biology written by M.R.S. Rao and published by Springer. This book was released on 2017-08-16 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: This contributed volume offers a comprehensive and detailed overview of the various aspects of long non-coding RNAs and discusses their emerging significance. Written by leading experts in the field, it motivates young researchers around the globe, and offers graduate and postgraduate students fascinating insights into genes and their regulation in eukaryotes and higher organisms.
Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Antisense Drug Technology written by Stanley T. Crooke and published by CRC Press. This book was released on 2007-07-25 with total page 848 pages. Available in PDF, EPUB and Kindle. Book excerpt: Extensively revised and updated, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition reflects the logarithmic progress made in the past four years of oligonucleotide-based therapies, and, in particular, antisense therapeutics and research. Interpreting lessons learned from the clinical trials of first generati
Download or read book Targeting RNA with Small Molecules written by Nicole Therese Schirle and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA serves many vital functions in biology. Therefore, the design of RNA-binding small molecules would serve as important tools for the study of gene expression and RNA interference. A major aim of this thesis work is the design of quinoline-based helix-threading peptides (HTPs) that can bind double-stranded RNA via threading intercalation. Ring closing metathesis was used to generate a small library of cyclic HTPs, which vary in peptide sequence and stereochemistry of the alpha-carbon of amino acid residues. A thiazole orange displacement assay was developed for screening HTP binding to an in vitro selected RNA aptamer binding site. Results showed that binding affinity is dependent on peptide sequence and amino acid stereochemistry. Despite RNA mapping with EDTA-Fe modified HTPs, little is known about the contacts HTPs make with their RNA targets. A self-complementary single strand of RNA was designed to anneal with itself forming two HTP binding sites. In collaboration with Professor Andrew Fisher, crystals of an HTP/RNA complex diffracted to 2.95 Å at Stanford Synchrotron Radiation Lightsource (SSRL). Furthermore, the RNA-binding domain of the U1A spliceosomal protein was expressed and purified for use in aptamer crystallization. Moreover, we have moved away from in vitro selected aptamers to focus on an mRNA coding for the serotonin 5HT2C̳ receptor protein. This RNA made an interesting HTP target for two reasons: 1) it is an adenosine-to-inosine RNA editing substrate, and 2) it should have a binding site for HTPs. A short duplex RNA containing several editing sites and loop region likely to be a target for HTPs was designed for quantitative S1 footprinting. We utilized hydroxyl radical affinity cleavage to characterize binding specificity of cyclic HTPs for this RNA target and found that cyclic HTPs selectively target the serotonin RNA. Furthermore, cyclic HTPs were shown to bind the serotonin RNA and were capable of substrate-selective inhibition of RNA editing. Finally, the pre-mRNA coding for the DNA repair enzyme Neil1 was shown to be a substrate the adenosine deaminase that acts on RNA 1 (ADAR1). Editing of this novel substrate was characterized and treatment of glioma cells with interferon resulted in increased editing of Neil1 pre-mRNA in vivo.
Download or read book Plant Small RNA written by Praveen Guleria and published by Academic Press. This book was released on 2020-02-19 with total page 638 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plant Small RNA: Biogenesis, Regulation and Application describes the biosynthesis of small RNA in plant systems. With an emphasis on the various molecular mechanisms affected by small RNA and their applications in supporting plant growth and survival, this books presents the basics and most recent advancements in small RNA mediated plant genomics, metabolomics, proteomics and physiology. In addition, it emphasizes the various molecular mechanisms affected by small RNA and their applications in supporting plant growth and survival. Final sections cover the most recent advancements in small RNA mediated plant genomics, metabolomics, proteomics and physiology. - Presents foundational information about small RNA biology and regulation in plants - Includes small RNA pathway advances - Describes the application and scope of small RNA technology for agricultural stability
Download or read book RNA Activation written by Long-Cheng Li and published by Springer. This book was released on 2017-06-19 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers an essential guide to RNA activation (RNAa), an emerging and fascinating new field. RNAa is a small RNA-guided and Argonaute-dependent gene regulation phenomenon in which promoter-targeted short double-stranded RNAs (dsRNAs) induce target gene expression at the transcriptional level. It occurs primarily in the nucleus and can be mediated by artificially designed short duplex RNAs that target regulatory sequences (e.g., promoters, genes’ 3’ termini and enhancers) and naturally occurring small RNAs (e.g., miRNAs and C. elegans 22G-RNAs). With contributions from internationally respected RNA experts, this book provides comprehensive coverage of different RNAa mechanisms and a timely update on recent advances in RNAa research, with a focus on developing RNAa-based therapeutics. Special chapters are also devoted to the topics of gene activation induced by antisense oligonucleotides and the CRISPR system. As the first book to cover RNAa, it will be of interest to a wide audience, from scientists in academia and the pharmaceutical industry to clinicians who wish to further explore the biology of RNAa and related phenomena, so as to harness their full potential for use in biotechnology and drug development.
Download or read book Cell Polarity and Subcellular RNA Localization written by Dietmar Richter and published by Springer Science & Business Media. This book was released on 2012-11-03 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: Selective cytoplasmic organelle and protein targeting has long been thought to constitute the sole determinant of cell polarity and complexity. This view has been changed, however, by the discovery of differential subcellular RNA distribution patterns. Over the past decade it has become clear that selective mRNA sorting and translation contributes to an accumulation of cognate proteins at discrete cellular sites. In this book, various systems are discussed (e.g. Xenopus oocytes, mammalian brain, invertebrate nervous system) in terms of RNA trafficking, RNA-targeting sequences (cis-elements) and RNA-transporting proteins (trans-factors), activity-dependent translational regulation and the significance of the cytoskeleton for neuronal function and plasticity. It also discusses nucleocytoplasmic export of mRNA and viral RNA as another example of subcellular RNA kinesis.
Download or read book CRISPR Cas Systems written by Rodolphe Barrangou and published by Springer Science & Business Media. This book was released on 2012-12-13 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: CRISPR/Cas is a recently described defense system that protects bacteria and archaea against invasion by mobile genetic elements such as viruses and plasmids. A wide spectrum of distinct CRISPR/Cas systems has been identified in at least half of the available prokaryotic genomes. On-going structural and functional analyses have resulted in a far greater insight into the functions and possible applications of these systems, although many secrets remain to be discovered. In this book, experts summarize the state of the art in this exciting field.
Download or read book Targeting Structured RNA in Viruses written by Austin Yu and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug discovery in the last century has largely been dominated by therapeutics targeting proteins. RNA targeting has remained largely elusive and high-risk, but some recent therapeutics have seen great utility and success. One area where RNA targeting has strong potential is in tackling viral infections. Many viruses, especially RNA viruses have high rates of mutation that sometimes confer treatment resistance. A method to counter the high mutation rates of viruses is to develop treatments which target conserved regions of the viral genome that are highly structured. For my studies, two structured RNA targets were probed: the Zika virus (ZIKV) stem loop A (SLA) and the SARS-CoV-2 RNA pseudoknot. Replication of mosquito-borne pathogenic flaviviruses like Zika virus depends on a noncoding RNA motif in the 5' untranslated region of the genome which recruits the viral NS5 replicase. The three-dimensional architecture of the replication promoter RNA is termed the SLA. Sequence alignment as well as conservation and covariation analyses as evidence support a canonical RNA three-way junction (3WJ) architecture for the SLA RNA. The SLA 3WJ also influences viral translation by interaction with the E protein coding region and the conformational flexibility of the SLA 3WJ may be exploited to discover selectively binding ligands that interfere with viral replication. As a proof of concept, antisense DNA ligands hybridized at a domain of the SLA RNA served as surrogate ligands eliciting an extensive conformational change in the 3WJ fold which is readily detected by measuring FRET response. The FRET binding assay provides a useful tool for the discovery of small molecule ligands that target the flavivirus replication promoter. Another FRET binding assay was utilized to discover ligands which selectively bind the SARS-CoV-2 RNA pseudoknot. The discovered ligands consisted of aminoglycosides such as tobramycin and were retested with a phenotypic in vitro translation assay to assess for physiological relevance. While the results were not physiologically relevant, the discovered ligands act as a foundation for future work for discovering pan-SARS-CoV-2 mutant treatments and highlight the potential in targeting structured RNA as a drug target.
Download or read book Synthesis of Small Molecules Targeting RNA written by Qi Liu and published by . This book was released on 2004 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Innovative Medicine written by Kazuwa Nakao and published by Springer. This book was released on 2015-10-13 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
Download or read book RNA RNA Interactions written by Frank J. Schmidt and published by Humana Press. This book was released on 2014-10-29 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this volume expert researchers in the field detail many of the methods which are now commonly used to study RNA. These methods are presented as a guidebook to scientists who are experienced with RNA research and want to brush up on a new technique. 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 key tips on troubleshooting and avoiding known pitfalls. Thorough and intuitive, RNA-RNA Interactions: Methods and Protocols guides scientists investigating biological systems and studying RNA.
Download or read book Molecular Mechanisms and Applications of RNA Targeting CRISPR Endonucleases written by Alexandra East Seletsky and published by . This book was released on 2017 with total page 131 pages. Available in PDF, EPUB and Kindle. Book excerpt: Evolutionary pressure to protect against phage-induced lysis and rampant horizontal gene transfer has created a wide repertoire of defensive pathways in bacteria. CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated) systems are adaptive immune pathways that use RNA-guided nucleases to direct cleavage of invading nucleic acids. The programmable nature of these enzymes has enabled a revolution for DNA-targeting applications including gene editing, transcriptional control, and genomic imaging. In addition to DNA-targeting enzymes, specific subtypes of CRISPR-Cas systems recognize and degrade single stranded RNA (ssRNA) substrates. Repurposing these ssRNA-targeting enzymes into biotechnological tools is currently limited by a lack of mechanistic information. In this work, we address this issue by redirecting a well-studied DNA-targeting CRISPR nuclease, Cas9, to ssRNA targets and investigating the enzymatic mechanisms of a novel ssRNA-targeting CRISPR nuclease, Cas13a (formerly C2c2). Typically, Cas9 ignores ssRNA while searching for dsDNA targets due to ssRNA's inherent single-stranded structure and lack of a protospacer adjacent motif (PAM). We redirected Cas9 to bind and recognize ssRNA targets through addition of a third component, a target-complementary DNA oligonucleotide or PAMmer, that provides a DNA:RNA hybrid PAM. Using primary microRNAs as a model system, we provide proof-of-concept evidence that Cas9:PAMmer complexes can mediate the isolation and subsequent mass spectrometry analysis of protein complexes bound to specific RNAs. The complexity of redirecting Cas9 to ssRNA substrates motivated us to investigate CRISPR proteins that natively target RNA. We focused on Cas13a, a predicted ribonuclease from Type VI CRISPR-Cas systems. We discovered that Cas13a possesses two distinct catalytic activities, one for site-specific cleavage of its CRISPR RNA (crRNA) and the second for nonspecific ssRNA degradation activated by target binding. These insights allowed us to establish a revised model for ssRNA-targeting by Type VI CRISPR-Cas systems. Through biochemical characterization of the entire Cas13a protein family, we revealed hidden diversity in substrate preferences and defined orthogonal enzyme subfamilies. These diverse Cas13a homologs can be harnessed in parallel for detection of distinct RNA species within complex mixtures for both bacterial immunity and diagnostic applications. Together, this work presents two novel biotechnological applications of CRISPR-Cas nucleases for RNA isolation and RNA detection.¬¬
Download or read book RNA Recognition written by and published by Academic Press. This book was released on 2019-06-23 with total page 470 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA Recognition, Volume 623, the latest volume in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. This updated volume covers a variety of topics, including The Preparation of cooperative RNA recognition complexes for crystallographic structural studies, Methods for thermal denaturation studies of fluorogenic aptamers, Dynamic combinatorial chemistry as a rapid, fragment-based approach to RNA-targeted compound discovery, Using a click chemistry assay to identify natural product ligands for pre-microRNAs, Lessons from exploration of chemical and structural small molecule:RNA space, Using ligand-observed NMR to study RNA-small molecule interactions, and much more. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Methods in Enzymology series - Includes the latest information on RNA Recognition
Download or read book RNA Therapeutics written by Paloma H. Giangrande and published by Academic Press. This book was released on 2022-04-10 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA Therapeutics: The Evolving Landscape of RNA Therapeutics provides a comprehensive overview of RNA therapeutic modalities, from bench-to-bedside, with an emphasis on the increasingly impactful areas of gene therapy, oligonucleotide therapeutics, gene editing and delivery. International leaders in the field examine RNA-based therapeutics tools that have been developed to-date to modulate cellular processes such as transcription, translation and protein function. Approved RNA-based therapies and lessons learned from failed therapies are discussed in-depth, as are evolving advances in RNA biochemical analysis, and similar advances that are enabling clinical application of RNA-based therapies. Later sections discuss delivery technologies, remaining hurdles in research and translation, the therapy development process from the lab to the clinic, and novel RNA-based therapies currently in development. - Features leading experts in the field of RNA therapeutics, spanning all classes of RNA therapies - Provides a detailed examination of approved RNA therapies and lessons learned from failed therapeutics - Covers all aspects of therapeutic discovery and preclinical development, as well as clinical translation, manufacturing and regulatory aspects
