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This book explores the role of miRNA as therapeutic agents, the progress made in this direction and the problems that need to be addressed for miRNA based therapies to become successful. It also discusses the basic biology of miRNA sythesis, regulation, and their role in disease biology.

Translating microRNA to the Clinic reviews the possibilities of current methodological tools and experimental approaches used by leading translational researchers. The book features the uses of micro ribonucleic acid as deployed in cancer targeting in biomarkers, diabetes, cardiovascular disease, and neurodegeneration, among many others. Pedagogically, the work concentrates on the latest knowledge, laboratory techniques, and experimental approaches used by translational research leaders in this field, promoting a cross-disciplinary communication between the sub-specialities of medicine, but in common with other books on the topic. In addition, the book emphasizes recent innovations, critical barriers to progress, the new tools that are being used to overcome them, and specific areas of research that require additional study to advance the field as a whole. Encompasses the latest innovations and tools being used to apply microRNA from lab to clinic< Extensive pedagogical updates aiming to improve the education of translational researchers in this field Transdisciplinary approach aims to support cross-fertilization between different sub-specialties of medicine

In recent years, understanding of microRNA (miRNA) biogenesis, the molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has expanded. Mapping of Nervous System Diseases via MicroRNAs provides an up-to-date review on the function of miRNA in neurological diseases as well as advancements in technology for

MicroRNAs as the endogenous mediators of RNA interference have experienced an unprecedented career in recent years, highlighting their pathogenic, diagnostic and potential therapeutic relevance. Beside tissue microRNAs, they are also found in body fluids, most notably in blood. Significant differences of circulating microRNA levels have been found in various diseases, making them candidates for minimally invasive markers of disease, for example tumor malignancy. The book focuses on the potential diagnostic applicability of circulating microRNAs in various diseases and their potential biological significance.

This volume explores microRNA function in a wide array of human disorders, providing a clinical basis for precision medicine and personalized therapies using these molecules. The twenty-one chapters, all authored by internationally-renowned experts, open with an introduction contextualizing microRNA manipulation within today's initiatives towards precision medicine. The following chapters explore the clinical role of microRNAs in the diagnosis and treatment of metabolic and cardiovascular disorders, focusing on mitochondrial fitness, arterial hypertension, cardiovascular remodeling, cerebrovascular disease, pulmonary hypertension, diabetic kidney disease, and kidney transplantation. The subsequent chapters discuss the importance of microRNAs in the wound healing process and in skin disease, in the pathogenesis of allergy, in human ovulation, and in infection. The book concludes with chapters which outline the emerging role of microRNAS in doping and detail microRNA profiling.microRNA: Medical Evidence is an ideal companion to both microRNA: Basic Scienceand microRNA: Cancer. Taken together, these three books provide a state-of-the-art overview of this rapidly-expanding and fascinating field, from themolecular level to clinical practice. It will be invaluable to medical students, physicians, and researchers, as a complete and unique guide in the exploration of microRNA in basic science, cancer and clinical practice.

This volume explores microRNA pathophysiology, focusing on basic concepts in molecular and cellular biology. Chapters contributed by leading scientists examine recently discovered pathways in several processes, including aging, diabetes, cardiovascular disease, hematopoiesis, and mitochondrial fitness. The authors contextualize microRNAs within epigenetics and micropeptidomics, angiongenesis and atherosclerosis, endometrial pathophysiology, and more. Throughout, numerous color photographs, diagrams of molecular pathways, and tables enhance the text.microRNA: Basic Science is an ideal companion to both microRNA: Medical Evidenceand microRNA: Cancer. Taken together, these three books provide a state-of-the-art overview of this rapidly-expanding and fascinating field, from the molecular level to clinical practice. It will be invaluable to medical students, physicians, and researchers, as a complete and unique guide in the exploration of microRNA in basic science, cancer and clinical practice.

Aberrant expression and function of microRNAs (miRNAs) in cancer have added a new layer of complexity to the understanding of development and progression of the disease state. It has been demonstrated that miRNAs have a crucial function in oncogenesis by regulating cell proliferation and apoptosis as oncogenes or tumor suppressors. The expression signatures of miRNAs provide exciting opportunities in the diagnosis, prognosis and therapy of cancer. Since miRNAs can function as either oncogenes or tumor suppressor genes in oncogenesis, the potential of using these small RNAs as therapeutic targets opens up new opportunities for cancer therapy by either inhibiting or augmenting their activity.

During the past decade it has become evident that microRNAs regulate gene expressions and control many developmental and cellular processes in eukaryotic organisms. Recent studies suggest that microRNAs play an important role in toxicogenomics and are likely to play an important role in a range of human diseases including cancer. microRNAs in Toxicology and Medicine is a comprehensive and authoritative compilation of up-to-date developments in this emerging research area, presented by internationally recognized investigators. It focuses on the role of microRNA in biology and medicine with a special emphasis on toxicology. Divided into six parts, topics covered include: microRNA and toxicology – including environmental toxicants and perturbation of miRNA signaling; microRNA, and Disease States featuring microRNAs in drug-induced liver toxicity, microRNAs and Inflammation the regulatory role of microRNA in mutagenesis, microRNAs and cancer, and the role of microRNAs in tumor progression and therapy, as well as current understanding of microRNAs as therapeutic targets in cancer microRNAs and disease states microRNAs and stem cells microRNAs and genomics microRNAs and epigenomics microRNAs and biomarkers – including body fluid microRNAs as toxicological biomarkers, cell-free microRNAs as biomarkers in human diseases, and circulating microRNAs as biomarkers of drug-induced pancreatitis microRNAs in Toxicology and Medicine is an essential insight into the current trends and future directions of research in this rapidly expanding field for investigators, toxicologists, risk assessors, and regulators in academia, medical settings, industry, and government.

This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers research methods in riboswitch discovery and validation, synthesis and sample prep methods for large RNAs, riboswitch structure and function methods, folding pathways and dynamics, and ligand interactions and thermodynamics. Continues the legacy of this premier serial with quality chapters authored by leaders in the field Covers research methods in riboswitch discovery, structure and function Contains sections on such topics as riboswitch discovery and validation, synthesis and sample prep methods for large RNAs, riboswitch structure and function methods, folding pathways and dynamics, ligand interactions and thermodynamics

MicroRNAs in Medicine provides an access point into the current literature on microRNA for both scientists and clinicians, with an up-to-date look at what is happening in the emerging field of microRNAs and their relevance to medicine. Each chapter is a comprehensive review, with descriptions of the latest microRNA research written by international leaders in their field. Opening with an introduction to what microRNAs are and how they function, the book goes on to explore the role of microRNAs in normal physiological functions, infectious diseases, non-infectious diseases, cancer, circulating microRNAs as non-invasive biomarkers, and finally their potential as novel therapeutics. Including background information on the field as well as reviews of the latest research breakthroughs, MicroRNAs in Medicine is a one-stop source of information to satisfy the specialists and non-specialists alike, appealing to students, researchers, and clinicians interested in understanding the potential of microRNAs in medicine and research.

MicroRNA (miRNA) biology is a cutting-edge topic in basic as well as biomedical research. This is a specialized book focusing on the current understanding of the role of miRNAs in the development, progression, invasion, and metastasis of diverse types of cancer. It also reviews their potential for applications in cancer diagnosis, prognosis, and th

The enormous potential of siRNA as a therapeutic has led to an explosion of interest from the scientific community. There has been intense interest from Big Pharma to capitalise on this new technology but the fact remains that delivery is a key determinant in realizing the full clinical potential of RNA interference. There is an urgent need for better delivery methods to take this technology forward. This book addresses the role of different RNAi molecules in cellular processes as rational for diagnostic and therapeutic approaches. This book will cover RNAi therapeutic design to optimize siRNA potency and reduce off-target effects and current delivery technologies to overcome both intracellular and extracellular barriers. The reader will gain an insight into RNA interference from the cellular mechanisms to screening to siRNA design right through to diagnostic and therapeutic applications.

MiRNA is an extremely fast growing field, and miRNA knowledge is now believed to be a pivotal element of cancer biology. It is already evident that the discovery of miRNA has created a paradigm shift in post-genomics biology, not only for scientists accustomed to traditional central dogma of molecular biology but also for researchers studying human diseases by the traditional genetics approach of studying one gene at the time. This book provides an introduction to the basic principles of miRNA biology, overview of miRNA significance in the hallmarks of cancer, experimental techniques used in miRNA research, and in special part - miRNAs importance in wide range of solid cancers with a special focus on its potential usage in molecular pathology, predictive oncology or as a novel therapeutic targets.

RNA Interference: Application to Drug Discovery and Challenges to Pharmaceutical Development provides a general overview of this rapidly emerging field, with a strong emphasis on issues and aspects that are important to a drug development team. The first part covers more general background of RNA interference and its application in drug discovery. In the second part, the book addresses siRNA (small interfering RNA), a pharmaceutically potent form, and its use and delivery in therapeutics along with manufacturing and delivery aspects.

MicroRNAs have recently emerged as key regulators of gene expression during development and are frequently misexpressed in human disease states, in particular cancer. These 22-nucleotide-long transcripts act to promote or repress cell proliferation, migration and apoptosis during development, all of which are processes that go awry in cancer. Thus, microRNAs have the ability to behave like oncogenes or tumor suppressors. In addition, their small size and molecular properties make them amenable as targets and therapeutics in cancer treatment. This book goes into detail on how microRNAs represent a paradigm shift in thinking about gene regulation during development and disease, and provide the oncologist with a potentially powerful new battery of agents to diagnose and treat cancer.

MicroRNAs are involved in crucial biological processes, including developmental timing, cell proliferation, apoptosis, and stress responses. This book presents topical research in the study of microRNAs, including their potential applications in aquaporin associated pathogenesis; microRNAs as novel biomarkers and therapeutic targets for cancer; microRNAs used in regulating EMT and blood circulation metastasis of lung cancer stem cells; the biological functions of microRNAs in animals and the regulation of metabolism, aging and lifespan by microRNAs.

This concise, self-contained and cohesive book focuses on commonly used and recently developed methods for designing and analyzing high-throughput screening (HTS) experiments from a statistically sound basis. Combining ideas from biology, computing and statistics, the author explains experimental designs and analytic methods that are amenable to rigorous analysis and interpretation of RNAi HTS experiments. The opening chapters are carefully presented to be accessible both to biologists with training only in basic statistics and to computational scientists and statisticians with basic biological knowledge. Biologists will see how new experiment designs and rudimentary data-handling strategies for RNAi HTS experiments can improve their results, whereas analysts will learn how to apply recently developed statistical methods to interpret HTS experiments.

RNAi technology is used for large-scale screens that systematically shut down each gene in the cell, which can help identify the components necessary for a particular cellular process or an event such as cell division. Exploitation of the pathway is also a promising tool in biotechnology and medicine. Introducing new technology in the study of RNA

The discovery of microRNAs has revealed an unexpected and spectacular additional level of fine tuning of the genome and how genes are used again and again in different combinations to generate the complexity that underlies for instance the brain. Since the initial studies performed in C.elegans, we have gone a far way to begin to understand how microRNA pathways can have an impact on health and disease in human. Although microRNAs are abundantly expressed in the brain, relatively little is known about the multiple functions of these RNA molecules in the nervous system. Nevertheless, we know already that microRNA pathways play major roles in the proliferation, differentiation, function and maintenance of neuronal cells. Several intriguing studies have linked microRNAs as major regulators of the neuronal phenotype, and have implicated specific microRNAs in the regulation of synapse formation and plasticity. Dysfunction of microRNA pathways is also slowly emerging as a potential important contributor to the pathogenesis of major neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. These novel insights appear to be particular promising for the understanding of the very frequent and badly understood sporadic forms of these diseases as compared to the genetic forms. Thus, the better understanding of the implications of this novel field of molecular biology is crucial for the broad area of neurosciences, from the fundamental aspects to the clinic, and from novel diagnostic to potentially therapeutic applications for severe neurological and maybe psychiatric diseases.

MicroRNAs (miRNAs), endogenous noncoding regulatory mRNAs of around 22-nucleotides long, have rapidly emerged as one of the key governors of the gene expression regulatory program in cells of varying species, with ever-increasing implications in the control of the fundamental biological processes and in the pathogenesis of adult humans. The exciting findings in this field have inspired us with a premise and a promise that miRNAs will ultimately be taken to the heart for therapy of human disease. While miRNAs have been considered potential therapeutic targets for disease treatment, it remains obscured what strategies we can use to achieve the goal. In the past years, we have witnessed a rapid evolving of many creative, innovative, inventive strategies and methodologies pertinent to miRNA research and applications. These technologies have convincingly demonstrated their efficacy and reliability in producing gain-of-function or loss-of-function of miRNAs through targeting miRNA expression/biogenesis/function, providing new tools for elucidating miRNA functions and opening up a new avenue for the development of new agents targeting miRNAs for therapeutic aims. The present book provides comprehensive descriptions of these technologies and their applications to miRNA research and to new drug design for miRNA-related diseases. It starts with an overview of up-to-date knowledge of miRNA biology and the potential of miRNAs as therapeutic targets for human disease, followed by an introduction of the new concept of miRNA interference (miRNAi) and the perspectives of miRNAi technologies in general terms. In the following, each chapter introduces one of the miRNAi technologies with detailed descriptions of state-of-the-art design, procedures, principles and applications to basic research, R and D and clinical therapy.

New Findings Revolutionize Concepts of Gene FunctionEndogenous small RNAs have been found in various organisms, including humans, mice, flies, worms, fungi, and bacteria. Furthermore, it's been shown that microRNAs acting as cellular rheostats have the ability to modulate gene expression. In higher eukaryotes, microRNAs may regulate as much as 50 p

In the last few years the major effect that RNAi has had in invertebrate systems like C.elegans and drosophila is beginning to take hold in mammalian systems through both single gene knockdown experiments and genome-scale screens. In the next decade, there will no doubt be both notable successes and failures as we attempt to apply this genetic tool to various biological problems for the first time in academia and industry. Through the introduction of RNAi, mammalian systems have finally gained admittance to the pantheon of model genetic systems.

One of the major recent discoveries in molecular and cellular biology is that small double-stranded RNA molecules selectively turn off gene expression in all types of cell, a phenomenon known as RNA silencing. This discovery led to the development of RNA interference (known as RNAi) as a powerful research tool in the functional study of individual genes and their products, and in functional genomics. In RNAi, specific small double-stranded RNA molecules (small interfering RNAs or siRNAs) are introduced into cells to selectively silence certain genes.RNAi covers the basic concepts and mechanisms of RNAi, transfection of cells with siRNAs, the design and validation of RNAi reagents, RNAi techniques in different organisms, large-scale RNAi screening, applications of RNAi in drug discovery, and potential uses of RNAi as a therapeutic agent. A key feature of RNAi is the highlighting of the pitfalls that can occur and how to minimize them. The book also contains a complete list of abbreviations.

Nearly 97% of the human genome is the non-coding DNA, which varies from one species to another, and changes in these sequences are frequently noticed to manifest clinical and circumstantial malfunction. Numerous non-protein-coding genes are recently found to encode microRNAs, which are responsible for RNA-mediated gene silencing through RNA interference (RNAi)-like pathways. MicroRNAs (miRNAs), small single-stranded 17–25 nucleotide RNAs capable of interfering with intracellular messenger RNAs (mRNAs) that contain either complete or partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. Currently over 1000 native miRNA species found in vertebrates and many more new miRNA homologs continue to be identified; however, most of their functions remain to be determined. In this book, many new perspectives of the miRNA research are reviewed and discussed, including their roles in stem cell maintenance, embryonic development, tissue differentiation, adult physiology, disease pathology, cancer research, viral infection, genetic engineering in plants, and utility in cosmetic applications. These new findings may not only provide significant insight into the various mechanisms of miRNAs but also offer a great opportunity in developing new therapeutic interventions.

MicroRNAs (miRNA) are tiny bits of genetic material that were unknown nearly 10 years ago but now represent an exciting field of study in biology. Upon their discovery, researchers revealed for the first time a new mechanism by which microRNA can stop the function of messenger RNA (mRNA) by literally cutting it in half, interfering with the normal function of specific messenger RNAs in gene expression. This'expression'of genes that code for essential proteins is essentially what controls whether a cell turns into a liver, lung, or brain cell, for example. Understanding what activates this process – or stops it – is a key to understanding the biological process and builds a foundation for advances in medicine and other fields. This volume in Methods in Enzymology presents valuable methods for studying MicroRNA, with three sections covering identification of MicroRNAs and their targets; MicroRNA expression, maturation and functional analysis; and MicroRNAs and disease.

It is now known that microRNA (miRNA), once thought to be junk, can suppress the expression of other genes and may be involved in numerous cellular processes, including cell proliferation, apoptosis, cell differentiation, and development. In MicroRNA Protocols, expert miRNA researchers explain its basic concepts and introduce the most advanced technologies and techniques for predicting screening, isolating, and assaying it. The authors provide diverse, novel, and useful descriptions of miRNAs in several species-including plants, worms, flies, fish, chicks, mice, and humans-and show how they have been employed to develop miRNA as a potential drug design tool. Highlights include miRNA and their target prediction by computer analysis, functional assays of miRNA in vitro and in vivo, and transgenic animal models using miRNA technologies. Additional chapters cover gene regulation, small RNA function, RNA interference mechanisms, and transgenetics. The protocols follow the successful Methods in Molecular Biology series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Eminently practical and cutting-edge, MicroRNA Protocols affords biomedical researchers readily reproducible techniques to understand and study the molecular pathogenesis of disease and design new therapeutic strategies.

In recent years Molecular Biology has experienced an unprecedented revolution by the discovery of functional small RNAs. The number of cellular processes in which non-coding RNAs are involved is growing rapidly and include gene regulation on the transcriptional, post-transcriptional and translational level. To complicate matters, these processes seem to be strongly interconnected on the one hand, and diverse among different organisms on the other. This volume describes strategies for the discovery and validation of small RNAs and provides a snapshot of our current understanding of the different mechanisms triggered by small RNAs.

The past decade has witnessed a true revolution in our understanding of how RNA molecules can reduce or silence gene expression, a process that holds great promise in basic research and for antiviral and anticancer applications. In RNA Silencing: Methods and Protocols, many of the most notable and distinguished researchers in the field describe in step-by-step detail their best methods for the design, preparation, and use of RNAs to reduce gene expression in cells and organisms. The techniques range widely and include methods addressing the biochemical aspects of the silencing machinery, RNA silencing in non-mammalian organisms, and the in vivo delivery of siRNAs and silencing vectors. There are also techniques for designing, preparing, and using RNAs to silence gene expression, for fine-tuning regulation by targeting specific isoforms of a given gene, and for the study and use of microRNAs. The protocols follow the successful Methods in Molecular Biology series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and state-of-the-art, RNA Silencing: Methods and Protocols offers today's laboratory investigators a host of optimized and validated techniques to study RNA silencing and translate its concepts into successful practical applications.

RNA Interference (RNAi) technology has rapidly become one of the key methods used in functional genomics. RNAi is used to block the expression of genes and create phenotypes that can potentially yield clues about the function of these genes. In the postgenomic era, the elucidation of the physiological function of genes has become the rate-limiting step in the quest to develop'gene-based drugs'and RNAi could potentially play a pivotal role in the validation of such novel drugs. In this overview, the basic concepts and applications of RNAi biology are discussed. Leading experts from both academia and industry have contributed to this invaluable reference. The volume is forwarded by Andrew Fire, one of the winners of the 2006 Nobel Prize for the discovery of RNA Interference.

In this completely updated and expanded edition of a classic bench manual, hands-on experts take advantage of the latest advances in ribozyme, DNAzyme, hammerhead ribozymes and derivatives, and RNA interference technologies to describe in detail the exciting and successful methods now available for gene inactivation in vitro and in vivo. Their optimized techniques employ hairpin ribozymes, DNAzymes, hammerhead ribozymes and derivatives, group I intron ribozymes, RNase P ribozymes, and siRNAs, as well as general methods for RNA structure analysis, delivery of oligonucleotides, and gene therapy. Also provided are novel methods for identifying accessible cellular mRNA sites; group I intron and RNAse P ribozyme protocols for effective design, selection, and therapeutic applications; and the latest RNAi methods for sequence-specific gene silencing in a wide variety of organisms. Additional techniques cover the analysis of ribozyme structures and conformational transitions using nucleotide analog interference mapping and fluorescence resonance energy transfer, the use of ribozymes in clinical and gene therapy, and the use of ribozymes and DNAzymes in rodent models of human disease. Each proven protocol includes a background introduction outlining the principle behind the technique, step-by-step instructions, lists of equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and up-to-date, Ribozymes and siRNA Protocols details for experienced and novice investigators alike the many exciting advances in our understanding of nucleic acid enzymes, as well as demonstrating how they may be used to analyze gene function and target validation, and to productively develop novel therapeutics for human diseases.