This volume describes our current understanding of the biological role of visual and non-visual arrestins in different cells and tissues, focusing on the mechanisms of arrestin-mediated regulation of GPCRs and non-receptor signaling proteins in health and disease. The book covers wide range of arrestin functions, emphasizing therapeutic potential of targeting arrestin interactions with individual partners.

Sendai virus (SeV) is not just a mouse pathogen but is evolving into a cutting-edge component of biotechnology. SeV reverse genetics originating from a pure academic need to settle long-held questions in the biology and pathogenicity of nonsegmented negative strand RNA viruses (Mononegavirales) is about to bear the impressive fruit of multipurpose cytoplasmic (non-integrating) RNA vectors. This book brings together in one source the SeV biology revealed by conventional approaches and reverse genetics, the methods to construct the first-generation SeV vector and to generate safer versions, and the applications in medical settings that have left or are about to leave the laboratory bench. The applications, which already are diverse and have high medical impact, include use as vaccine vectors against AIDS and respiratory virus infections, creation of BioKnife to resect malignant tumors, induction of "footprint (transgene) free" pluripotent stem cells, and gene therapy for peripheral arterial disease. These achievements-which are just a few of many examples-were attainable only after rigorously incorporating the rich knowledge of SeV biology that has accumulated during the several decades since the discovery of the virus. Application of SeV vector is certain to expand greatly because of its extremely high performance in transgene expression and its remarkable target cell breadth.

Examples from various organs and diseases illustrate the potential benefit obtained when both therapeutic approaches are combined with delivery strategies. Representing the combined effort of several leading international research and clinical experts, this book, Emerging Trends in Cell and Gene Therapy, provides a complete account on and brings into sharp focus current trends and state-of-the-art in important areas at the interface of cell- and gene-based therapies. This book addresses the current fragmented understanding regarding these two research areas and fills the vast unmet educational need and interest of both students and researchers in academia and industry. Main features of the book: * Biological aspects of stem cell sources, differentiation and engineering. * Application of microfluidics to study stem cell dynamics * Potential clinical application of stem cells and gene therapy to specific human disease. * Utilization of biomaterials and stem cells in regenerative medicine with particular emphasis on spinal cord repair, ligament and bone tissue engineering. * Biomimetic multiscale topography for cell alignment.

I entered the gene therapy field in the mid-1990s, being fascinated by the immense potential of genes as drugs for the treatment of human disease. Since then, I have experienced the ups and downs of this discipline, and tried to contribute with my work and that of my laboratory to the development of innovative approaches to the treatment of cardiovascular disorders. During these years, I have had several opp- tunities to speak on gene therapy at lectures and academic lessons, and have often noticed that the field is very attractive to scientists of all disciplines. However, as yet no comprehensive book on the subject has been published. Indeed, most books in the field are either a collection of gene transfer laboratory protocols or deal with the subject in a rather superficial manner. Hence the idea to write a gene therapy textbook that is broad and comprehensive, but at the same time provides sufficient molecular and clinical detail to be of interest to students, professors, and specialists in the various disciplines that contribute to gene therapy. I have tried to keep the language plain and, whenever possible, non-technical. Since the book is intended to be a textbook in the field of gene therapy in both the basic science and clinical areas, whenever technical descriptions are required, they are provided.

In this book internationally recognized investigators describe cutting-edge laboratory techniques for the study of Production and In Vivo Applications of Gene Transfer Vectors and Design and Characterization of Gene Transfer Vectors. Readers will find a comprehensive resource of current and emerging methods for the production of viral and non-viral gene transfer vectors, as well as detailed protocols for applications in stem cell biology, cancer research and infectious disease.

Introduction.-Probing Astrocyte Function in Fragile X Syndrome.- Neural Stem Cells.- Fragile X Mental Retardation Protein (FMRP) and the Spinal Sensory System. The Role of the Postsynaptic Density in the Pathology of the Fragile X Syndrome.- Behavior in a Drosophila model of Fragile X.- Molecular and Genetic Analysis of the Drosophila Model of Fragile X Syndrome.- Fragile X Mental Retardation Protein and Stem Cells.- Manipulating the Fragile X Mental Retardation Proteins in the Frog.- Exploring the Zebra finch Taeniopygia gutta as a Novel Animal Model for the Speech-language Deficit of Fragile X Syndrome.- Neuroendocrine Alterations in the Fragile X Mouse.- Taking STEPs forward to understanding Fragile X Syndrome.- Fmr-1 as an Offspring Genetic and a Maternal Environmental Factor in Neurodevelopmental Disease.- Mouse Models of the Fragile X Premutation and the Fragile X Associated Tremor/Ataxia Syndrome.- Clinical Aspects of the Fragile X Syndrome.- Fragile X Syndrome: A Psychiatric Perspective.- Fragile X Syndrome and Targeted Treatment Trials.- The Fragile X-associate Tremor Ataxia Syndrome.- Vignettes: Models in Absentia."

Androgens and androgen receptors (AR) play critical roles in the development and progression of prostate cancer, the most frequently diagnosed cancer and second leading cause of cancer death in US males. AR is an androgen-dependent DNA-binding transcription factor that regulates the expression of androgen-responsive genes. Identification and characterization of androgen-responsive genes provide insights into the cellular mechanisms of androgen action and may lead to new approaches in diagnosis, prognosis, prevention and/or treatment of prostate cancer. This volume provides critical information from well respected experts in the field. Some of the exciting topics include the new understanding of mechanisms underlining the regulation of androgen-responsive gene expression, and functions of various androgen-responsive genes in biological processes essential in carcinogenesis including cell growth, angiogenesis, and epithelial-to-mesenchyme transition (EMT). Other important aspects addressed are the current and potential clinic applications of knowledge on androgen-responsive gene regulation and function. This book is intended for researchers, scientists, faculty, and advanced graduate students with an interest in androgen action and prostate cancer.

This book is a collection of preclinical and clinical reports on the appli cation of gene therapy to human disease. The focus of these studies is on cancer and cardiovascular disease. There are two fundamental technologies for delivering therapeutic genes to diseased ceHs: either viral vectors, as discussed by Dr. Bal main, or non-viral vector systems, as discussed by Dr. Felgner. The strengths and limitations of each of these delivery systems are charac terized. The use of a therapeutic gene to treat a disease has taken two general approaches. The first is to introduce anormal (i. e., wild type) gene into the patient that will restore normal gene function. Dr. Weiss man has characterized the tumor suppressor gene (pS3), and has shown that it can restore normal ceH function in cancer cells. The second ap proach is to treat the disease with antisense molecules. Abnormal gene expression can be down-regulated and selectively inhibited by anti sense molecules, which can reverse the pathologie process in cancer cells. Dr. Gewirtz has demonstrated this with anti sense genes on leuke mia, while Dr. Scanlon has applied this principle using ribozymes in human carcinomas. During this symposium, Dr. Engler described clinical studies of gene therapy using growth factors to stimulate new blood vessels in patients with cardiovascular disease. Several gene therapy strategies were used for cancer: overcoming drug resistance by Dr. Bertino, a pro-drug strategy with ganciclovir by Dr."

Biotechnology harnesses cellular and biochemical systems to advance knowledge of the molecular cause of disease and to provide new diagnostic tools and more precisely targeted drugs. Within a decade, global investment in medical biotechnology has increased more than ten-fold, resulting in therapies for previously untreatable conditions. But what exactly is biotechnology and what are its origins? What further benefits to human health could it offer in the future? Written in an accessible style, contributors to this book explore the history behind different biotechnology tools, how they are used, and how they are reshaping the future of diagnostics, therapeutics and vaccines. Among the technologies examined are genetic engineering, DNA sequencing, monoclonal antibodies, stem cells, gene therapy, cancer immunotherapy and the most recent newcomer - synthetic biology. Applying new biotechnologies in medicine is not without great challenges. As medicines shift from small organic molecules to large, complex structures, such as therapeutic proteins, drugs become difficult to make, administer and regulate. This book will intrigue anyone interested in medicine and how we have been, and may continue to, engineer better health for ourselves. Such changes have major implications for how and where drugs are manufactured, the cost of medicine and the ethics of how far society is prepared to go to combat disease.

During the first half century of genetics, coinciding with the first half of this cen tury, geneticists dreamt of the repair of genetic disease by altering or replacing defective genes. H. J. Muller wrote of the great advantages of mutations, "nanoneedles" in his apt term, for delicately probing physiological and chemical processes. In the same spirit, genes could be used to provide treatments of needle point delicacy. Yet, during this period no realistic possibility appeared; it remained but a dream. The situation changed abruptly at the half century. Microbial genetics and its offshoot, cell culture genetics, provided the route. Pneumococcus transformation showed that exogenous DNA could become a permanent part of the genome; yet attempts to reproduce this in animals produced a few tantalizing hints of success, but mostly failures. Transduction, using a virus as mediator, offered a better op portunity. The fITSt reproducible in vivo gene therapy in a whole animal came in 1981. This was in Drosophila, with a transposable element as carrier. Flies were "cured" of a mutant eye color by incorporation of the normal allele, and the effect was transmissible, foreshadowing not only somatic, but germ line gene therapy. At the same time, retroviruses carrying human genes were found to be ex tremely efficient in transferring their contents to the chromosomes of cultured cells."

This book has been written in response to the many physicians and scien tists working on the development of biological approaches to providing therapies for many orthopaedic disorders as well as to improving the healing of many tissues of the musculoskeletal system. The first goal of this book is to make the language compatible between the bench scientist and the clinician working in orthopaedic and sports medicine in order to cover specific areas of the orthopaedic discipline where the treatment can be improved and/or changed by the advancements in molecular medicine. Advancements in molecular biology, which encompass the study of the genetic basis of disease, have produced new diagnostic methods and drug therapies for genetic diseases and acquired disorders. The growth in the understanding of human genetics has also led to the initiation of many human gene therapy experiments. Although many approved therapeutic clinical trials using this new technology have been performed in the last ten years, the first clinical trial using this technology in the area of orthopaedics was performed at the University of Pittsburgh."

In this monograph about gene therapy of autoimmune and inflammatory d- orders we have gathered international experts and leaders from different fields to review the state of the art advances on topics ranging from disease entities to vectors and engineered cells. The different approaches described in each chapter take into consideration the biomedical knowledge of these diseases and address the complexities of delivering long-term genetic interventions. Gene therapy also serves as a testing ground for new therapeutic entities and helps provide proof of principle for their potential therapeutic role in animal models of disease. Scaling up from mice to men still remains an important h- dle not only from the quantitative point of view, but also for currently unknown and unexpected secondary effects of the vector or the transgene. Some of these approaches have already been tested in the clinic, but much more needs to be done to understand the human conditions treated and the n- ural history of their pathology. We are indebted to the secretarial assistance of Ms. Lin Wells (Bone and Joint Research Unit, London, UK) and the help of Hans Detlef Kluber for his help in getting this book published. We hope this book will be of interest to c- nicians and scientists and inspiring to students of the subject who will use their own ingenuity and knowledge to further forward this discipline into clinical use.

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.

This set reports the results of the 10th International Histocompatibility Workshop, in which 362 laboratories collaborated over a three year period in research projects on the classification of HLA genes and their products. "Volume 1" describes the experimental design of the workshop studies and their results. "Volume 2" is a collection of papers on the latest developments in the molecular biology of HLA systems. Immunobiology of HLA is a valuable reference for tissue typing laboratories, blood banks, and general research programs on HLA and related diseases because it identifies common sources of HLA genes and gene products to be used as reference reagents, and because it is the only complete compilation of the latest research and results in the field.

'[A]n excellent, brisk guide to what is likely to happen as opposed to the fantastically remote.' - Los Angeles Review of Books In 2018 the world woke up to gene editing with a storm of controversy over twin girls born in China with genetic changes deliberately introduced by scientists - changes they will pass on to their own offspring. Genetic modification (GM) has been with us for 45 years now, but the new system known as CRISPR or gene editing can manipulate the genes of almost any organism with a degree of precision, ease and speed that we could only dream of ten years ago. But is it ethical to change the genetic material of organisms in a way that might be passed on to future generations? If a person is suffering from a lethal genetic disease, is it unethical to deny them this option? Who controls the application of this technology, when it makes 'biohacking' - perhaps of one's own genome - a real possibility? Nessa Carey's book is a thrilling and timely snapshot of a cutting-edge technology that will radically alter our futures and the way we prevent disease. 'A focused snapshot of a brave new world.' - Nature 'A brisk, accessible primer on the fast-moving field, a clear-eyed look at a technology that is already driving major scientific advances - and raising complex ethical questions.' - Emily Anthes, Undark

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.

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions. This book series 'Cell Biology and Translational Medicine (CBTMED)' as part of SpringerNature's longstanding and very successful Advances in Experimental Medicine and Biology book series, has the goal to accelerate advances by timely information exchange. Emerging areas of regenerative medicine and translational aspects of stem cells are covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the seventh volume of a continuing series. Chapter "Application of iPSC to Modelling of Respiratory Diseases" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book reviews the current state of ocular drug therapy and future therapeutic opportunities for a wide variety of conditions, including Age-related Macular Degeneration, Diabetic Retinopathy and Macular Edema, Glaucoma, and Inherited Retinal Diseases. Retinal diseases are major contributors to moderate or severe vision impairment in adults aged 50 years and older. The respective patient populations for many of these indications is expected to significantly increase as the world population continues to grow older. An improved understanding of the etiological underpinnings of ocular degenerative diseases over the past decade has significantly bolstered ophthalmic drug discovery. In this volume, contributions from leading experts explore the unique challenges faced for ocular drug discovery and delivery providing the reader with detailed information on ocular pharmacokinetics, in vitro, ex vivo and in vivo models for retinal disease pathology and emerging gene therapy treatments. The book is intended for all researchers and clinicians who wish to increase their knowledge on the latest findings in ocular drug therapy.

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions. This book series 'Cell Biology and Translational Medicine (CBTMED)' as part of SpringerNature's longstanding and very successful Advances in Experimental Medicine and Biology book series, has the goal to accelerate advances by timely information exchange. Emerging areas of regenerative medicine and translational aspects of stem cells are covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the eight volume of a continuing series.

This is a reference handbook for young researchers exploring gene and cell therapy. Gene therapy could be defined as a set of strategies modifying gene expression or correcting mutant/defective genes through the administration of DNA (or RNA) to cells, in order to treat disease. Important advances like the discovery of RNA interference, the completion of the Human Genome project or the development of induced pluripotent stem cells (iPSc) and the basics of gene therapy are covered. This is a great book for students, teachers, biomedical researchers delving into gene/cell therapy or researchers borrowing skills from this scientific field.

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions. This book series 'Cell Biology and Translational Medicine (CBTMED)' as part of SpringerNature's longstanding and very successful Advances in Experimental Medicine and Biology book series, has the goal to accelerate advances by timely information exchange. Emerging areas of regenerative medicine and translational aspects of stem cells are covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the sixth volume of a continuing series.

This book focuses on an "outside the box" notion by utilizing the powerful applications of next-generation sequencing (NGS) technologies in the interface of chemistry and biology. In personalized medicine, developing small molecules targeting a specific genomic sequence is an attractive goal. N-methylpyrrole (P)-N-methylimidazole (I) polyamides (PIPs) are a class of small molecule that can bind to the DNA minor groove. First, a cost-effective NGS (ion torrent platform)-based Bind-n-Seq was developed to identify the binding specificity of PIP conjugates in a randomized DNA library. Their biological influences rely primarily on selective DNA binding affinity, so it is important to analyze their genome-wide binding preferences. However, it is demanding to enrich specifically the small-molecule-bound DNA without chemical cross-linking or covalent binding in chromatinized genomes. Herein is described a method that was developed using high-throughput sequencing to map the differential binding sites and relative enriched regions of non-cross-linked SAHA-PIPs throughout the complex human genome. SAHA-PIPs binding motifs were identified and the genome-level mapping of SAHA-PIPs-enriched regions provided evidence for the differential activation of the gene network. A method using high-throughput sequencing to map the binding sites and relative enriched regions of alkylating PIP throughout the human genome was also developed. The genome-level mapping of alkylating the PIP-enriched region and the binding sites on the human genome identifies significant genomic targets of breast cancer. It is anticipated that this pioneering low-cost, high through-put investigation at the sequence-specific level will be helpful in understanding the binding specificity of various DNA-binding small molecules, which in turn will be beneficial for the development of small-molecule-based drugs targeting a genome-level sequence.

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions. With a goal to accelerate advances by timely information exchange, this new book series 'Cell Biology and Translational Medicine (CBTMED)' as part of SpringerNature's longstanding and very successful Advances in Experimental Medicine and Biology book series is launched. Emerging areas of regenerative medicine and translational aspects of stem cells will be covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the first volume of a continuing series.

This work was compiled to serve as a convenient source that covers a number of techniques (and details of their use) in the rather large field of nanomedicine, with special attention paid to gene delivery. As principal investigators working in the field of nanomedicine, we sought to put together the most current and relevant topics in gene delivery, imaging and evaluation systems. We expect the work to serve very well for scientists and graduate students in the nanomedicine field.

This book summarizes early pioneering achievements in the field of human neural stem cell (hNSC) research and combines them with the latest advances in stem cell technology, including reprogramming and gene editing. The powerful potential of hNSC to generate and repair the developing and adult CNS has been confirmed by numerous experimental in vitro and in vivo studies. The book presents methods for hNSC derivation and discusses the mechanisms underlying NSC in vitro fate decisions and their in vivo therapeutic mode of action. The long-standing dogma that the human central nervous system (CNS) lacks the ability to regenerate was refuted at the end of the 20th century, when evidence of the presence of neurogenic zones in the adult human brain was found. These neurogenic zones are home to human neural stem cells (hNSCs), which are capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. NSCs isolated from human CNS have a number of clinical advantages, especially the innate potential to differentiate into functional neural cells. Nevertheless, their full clinical exploitation has been hindered by limited access to the tissue and low expansion potential. The search for an alternative to CNS sources of autologous, therapeutically competent hNSCs was the driving force for the many studies proving the in vitro plasticity of different somatic stem cells to generate NSCs and their functional progeny. Now the era of induced pluripotent stem cells has opened entirely new opportunities to achieve research and therapeutic goals with the aid of hNSCs.