Advances in Nanomedicine for the Delivery of Therapeutic Nucleic Acids addresses several issues related to safe and effective delivery of nucleic acids (NAs) using nanoparticles. A further emphasis would be laid on the mechanism of delivery of NAs, the barriers encountered and the strategies adapted to combat them. An exhaustive account of the advantages as well shortcomings of all the delivery vectors being employed in delivery of various NAs will be provided. On final note the regulatory aspects of nanoparticles mediated NA would be discussed, with focus on their clinical relevance. The design and development of nucleic acid-based therapeutics for the treatment of diseases arising from genetic abnormalities has made significant progress over the past few years. NAs have been widely explored for the treatment of cancer and infectious diseases or to block cell proliferation and thereby caused diseases. Advances in synthetic oligonucleotide chemistry resulted in synthesis of NAs that are relatively stable in in vivo environments. However, cellular targeting and intracellular delivery of NAs still remains a challenge. Further development of NA-based therapeutics depends on the progress of safe and effective carriers for systemic administration. Nanomedicine has facilitated availability of vectors with diminished cytotoxicity and enhanced efficacy which are rapidly emerging as systems of choice. These vectors protect NAs from enzymatic degradation by forming condensed complexes along with targeted tissue and cellular delivery. During the past few years, a myriad reports have appeared reporting delivery of NAs mediated by nanoparticles. This book will provide an overview of nanoparticles being employed in the in vitro and in vivo delivery of therapeutically relevant NAs like DNA, siRNA, LNA, PNA, etc.

This issue of Hematology/Oncology Clinics will focus on Gene Therapy. Topics include, but are not limited to Historical Perspective and Current Renaissance, Integrating Vectors, Nonintegrating Vectors, Gene Editing, Conditioning Therapies for Autologous HSCT, Approaches to Immunodeficiency, Approaches to Hemoglobinopathy, Approaches to Hemophilia, Hematopoietic Gene Therapies for Neurologic and Metabolic Disease, Gene Therapy Approaches to HIV and other Infectious Diseases, HSC Approaches to Cancer, and Gene Modified T Cell Therapies for Cancer.

This issue of Physical Medicine and Rehabilitation Clinics of North America will cover regenerative medicine. Rapid advances in stem cell science are opening new avenues for drug discovery and may lead to new uses of stem cells for other musculoskeletal disorders. Artcles to be included are: Evidence-Based Regenerative Prolotherapy and Perineural Injection Approaches; Platelet Rich Plasma; Autologous Conditioned Serum; Stem Cell Considerations for the Clinician; Adipose Derived Stromal Vascular Faction and Stem Cell Use, as well as many others.

This book reviews stem cell behavior in the lung as it relates to regenerative medicine and stem cell therapeutics. Topics ranging from basic developmental mechanisms of various types of lung stem cells through the identification and properties of stem cell behavior and their potential applications in lung repair and regeneration, are discussed by an expert in the field. These discoveries are placed within the structural context of tissue and developmental biology in sections dealing with recent advances in understanding of developmental lung stem cell biology and behavior and their potential applications. Lung Stem Cell Behavior is essential reading for researchers in stem cell biology and regenerative medicine, patient advocates, undergraduate students, graduate students, and clinicians interested in cellular therapy and tissue engineering therapies.

What will our lives be like fifty years from now? What will we know about ourselves as humans, and how will that affect our lives? It's impossible to know the future for certain, but one thing we do know--perhaps nothing will alter our future more than the Genetics Revolution of the past thirty-five years. This book clarifies the history and examines the possible impact of five major areas of genetic research:

• The Human Genome Project and genetic engineering
• In vitro fertilization (IVF) and the technology of reproduction
• The Human Genome Diversity Project, which is studying the variation of the human genome
• Embryonic stem-cell research
• Cloning

Ever since the birth of molecular biology, the tantalizing possibility of treating disease at its genetic roots has become increasingly feasible. Gene therapy - though still in its infancy - remains one of the hottest areas of research in medicine. Its approach utilizes a gene transfer vehicle ('vector') to deliver therapeutic DNA or RNA to cells of the body in order to rectify the defect that is causing the disease. Successful therapies have been reported in humans in recent years such as cures in boys with severe immune deficiencies. Moreover, gene therapy strategies are being adapted in numerous biomedical laboratories to obtain novel treatments for a variety of diseases and to study basic biological aspects of disease. Correction of disease in animal studies, is steadily gaining ground, highlighting the immense potential of gene therapy in the medical profession.This book will cover topics that are at the forefront of biomedical research such as RNA interference, viral and non-viral gene transfer systems, treatment of hematological diseases and disorders of the central nervous system. Leading experts on the respective vector or disease will contribute the individual chapters and explain cutting-edge technologies. It also gives a broad overview of the most important gene transfer vectors and most extensively studied target diseases. This comprehensive guide is therefore a must-read for anyone in the biotechnology, biomedical or medical industries seeking to further their knowledge in the area of human gene therapy.

This volume discusses protocols, ranging from vector production to delivery methods, used to execute gene therapy applications. Chapters are divided into four parts, and cover topics such as design, construction, and application of transcription activation-like effectors; multi-modal production of adeno-associated virus; construction of oncolytic herpes simplex virus; AAV-mediated gene delivery to the mouse liver; and intrathecal delivery of gene therapeutics by direct lumbar puncture in mice. 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. Comprehensive and authoritative, Viral Vectors for Gene Therapy: Methods and Protocols is a valuable resource for researchers, clinicians, and students looking to utilize viral vectors in gene therapy experiments.

Gene Therapy for Viral Infections provides a comprehensive review of the broader field of nucleic acid and its use in treating viral infections. The text bridges the gap between basic science and important clinical applications of the technology, providing a systematic, integrated review of the advances in nucleic acid-based antiviral drugs and the potential advantages of new technologies over current treatment options. Coverage begins with the fundamentals, exploring varying topics, including harnessing RNAi to silence viral gene expression, antiviral gene editing, viral gene therapy vectors, and non-viral vectors. Subsequent sections include detailed coverage of the developing use of gene therapy for the treatment of specific infections, the principles of rational design of antivirals, and the hurdles that currently face the further advancement of gene therapy technology.

Every day, newspapers and television news programs present stories on the latest controversies over healthcare and medical advances, but they do not have the space to provide detailed background on the issues. Websites and weblogs provide information from activists and partisans intent on presenting their side of a story. But where can students - or even ordinary citizens - go to obtain unbiased, detailed background on the medical issues affecting their daily lives? This volume in the Health and Medical Issues Today series provides readers and researchers a balanced, in-depth introduction to the medical, scientific, legal, and cultural issues surrounding gene therapy and its import in today's world of healthcare. Gene Therapy is organized to provide researchers with easy access to the information they need: BLSection 1 provides overview chapters on the background information needed to intelligently understand the issues and controversies surrounding gene therapy, such as the history of theories of the gene and recent developments in clinical trials BLSection 2 offers capsule examinations of the contemporary issues and debates that provoke the most heated disagreements and misunderstandings, such as whether or not humans should "tinker" with genetic material and who pays for genetic therapies. BLSection 3 includes reference material on stem cells, including primary source documents from important players in the struggle over gene therapy, a timeline of important events, and an annotated bibliography of useful print and electronic resources. This volume in the Health and Medical Issues Today series provides everything a student requires to understand the issues involved in gene therapyand provides a springboard for further research into the issue.

Translational Regenerative Medicine is a reference book that outlines the life cycle for effective implementation of discoveries in the dynamic field of regenerative medicine. By addressing science, technology, development, regulatory, manufacturing, intellectual property, investment, financial, and clinical aspects of the field, this work takes a holistic look at the translation of science and disseminates knowledge for practical use of regenerative medicine tools, therapeutics, and diagnostics. Incorporating contributions from leaders in the fields of translational science across academia, industry, and government, this book establishes a more fluid transition for rapid translation of research to enhance human health and well-being.

The huge potential for gene therapy to cure a wide range of diseases has led to high expectations and a great increase in research efforts in this area, particularly in the study of delivery via viral vectors, widely considered to be more efficient than DNA transfection. In Viral Vectors for Gene Therapy: Methods and Protocols, experts in the field present a collection of their knowledge and experience featuring methodologies that involve virus production, transferring protocols, and evaluating the efficacy of gene products. While thoroughly covering the most popular viral vector systems of adenovirus, retrovirus, and adeno-associated virus, this detailed volume also explores less common viral vector systems such as baculovirus, herpes virus, and measles virus, the growing interest in which is creating a considerable demand for large scale manufacturing and purification procedures. Written in the highly successful Methods in Molecular Biology (TM) series format, many chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and vital tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Viral Vectors for Gene Therapy: Methods and Protocols provides basic principles accessible to scientists from a wide variety of backgrounds for the development of gene therapy viral products that are safe and effective.

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.

In this book, leading international experts analyze state-of-the-art advances in gene transfer vectors for applications in inherited disorders and also examine the toxicity profiles of these methods. The authors discuss the strengths and weaknesses of available vectors in the clinical setting, and specifically focus on the challenges and possible solutions that researchers are testing in order to improve the safety of gene therapy for genetic diseases. This comprehensive and authoritative overview of vector development is a necessary text for researchers, toxicologists, pharmacologists, molecular biologists, physicians, and students in these fields.

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.

Recent stem cell research has revealed that miRNA and RNAi-mediated gene regulation is one of the vital determinates controlling the state of cell differentiation, with the small RNAs serving as key elements involved in regulatory network control of pluripotent cell fate determination. In RNAi and microRNA-Mediated Gene Regulation in Stem Cells: Methods, Protocols, and Applications, expert authors from laboratories across the globe contribute an accessible compendium of up-to-date, proven methods focused on the study of the titular topic. Divided into three sections, the book first gives a brief introduction to RNAi and miRNAs in stem cells, with a focus on the current status of research and future perspectives, then it continues with detailed methods and protocols for RNAi screening, transfection, and the knockdown of specific genes and pathways in several animal species, including humans and mice, concluding with a section on recently developed methods for identification of miRNAs, including a general protocol for preparation and analysis of miRNA libraries for deep sequencing, knock down of a specific gene using miRNA-based shRNA, and miRNA expression analysis using qRT-PCR. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes highlighting tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, RNAi and microRNA-Mediated Gene Regulation in Stem Cells: Methods, Protocols, and Applications serves as a valuable resource for scientists and aspiring graduate students interested in the intersection of RNAi, miRNA, and stem cell molecular biology and the exciting areas of medicine, including regenerative medicine, aging, cancer, and neurological disorders, that can be advanced through this expanding area of research.

The possibility of treating cancer, a disease frequently defined by
genetic defects, by introducing genes that target these very
alterations has generated tremendous enthusiasm. This enthusiasm,
however, has been tempered by an increasing number of obstacles to
successful therapy, including vector systems that do not reach systemic
metastases, therapeutic genes with redundant mechanisms allowing for
cellular resistance, and toxicities in clinical trials that result in
premature closure. The three comprehensive sections of this volume
present currently available cancer gene therapy techniques, with
specific attention to these trouble spots. Part I describes the various
aspects of gene delivery including vehicles, or vectors, and their
respective characteristics and production methods. In Part II, the
contributors discuss strategies and targets for the treatment of
cancer, including methods for cell-death therapies, correction of
underlying genetic defects at the molecular level, and activation of
the immune system or tumor microenvironment. The contributors provide a
succinct framework for understanding the basic underlying oncogenic
changes, which encourages the development of vectors engineered to
exploit these gene mutations through selective spread of the vector in
tumor cells with the specific changes. Finally, in Part III, experts in
clinical gene therapy trials discuss the difficulties inherent in
bringing gene therapy treatment for cancer to the clinic, and principal
investigators present gene therapy approaches in the clinical testing
stage and the results that have reached the stage ofclinical
testing.of these trials.

MicroRNA research and development is the billion-dollar baby and most lucrative option for drug discovery in gene therapy industries worldwide. Personalized microRNA treatments are in many cases the only remedy for viral diseases that have no cure in conventional drugs and offer to bring us closer than ever to "personalized medicine." They also counteract cancer and other infectious and neuro-diseases. Early diagnosis, prognosis, staging, and sub-classification of various cancers can easily be facilitated by microRNA-based biomarkers. MicroRNA surveys recent advances in RNA and RNA-protein components that highlight RNA delivery, its stability, and applications of RNA-based drugs for the modulation of gene/protein expression and gene editing. The book not only focuses on the modern medicines of microRNA-based early diagnostic and therapy development, but also works as a hidden treasure for drug discovery of multiple rare diseases worldwide. It offers indispensable learning materials for academic researchers, graduate, and medical students, and offers a powerful practical guide for RNA-Pharma and gene therapy industries.

As the leading cause of adult disability, stroke poses substantial economic and psychological burdens to populations around the world. Against this dismal backdrop, several novel "neurorestorative" approaches are being investigated as adjunctive treatments to physiotherapy. Stroke Recovery with Cellular Therapies discusses the promising investigations around the world on cell-based therapies to enhance recovery from stroke. Throughout this groundbreaking text, chapters detail the potential benefits of various types of cells and approaches for ischemic and hemorrhagic stroke, and all studies rely upon traditional histological and functional outcomes. Among the topics detailed in this volume are transplanting immortalized neural stem cells, transplantation of bone marrow stromal cells, adipose-derived stem cells, endogenous neural stem cells in tissue remodeling, and an investigation into the ethics of stem cell research. This text provides an overview of the field, stimulates ideas for further research, and will help serve as a foundation for cell-based therapies to move forward as a viable approach for stroke recovery in the future.

Continued refinement ofwide-spread access to transgenic technology has allowed for new animal models have been developed that exhibit features of autoimmune disease have been developed that exhibit features of autoimmune disease. The second edition of "Autoimmunity: Methods and Protocols" researchers in the field detail many of the most up-to-date methods which are now commonly used to study autoimmunity. The first half the book focuses on methods and protocols used to assess immunological and biochemical pathways of diseases pathogenesis in human subjects. While the second half investigates treatment of inflammatory arthritis, experimental allergic encephalomyelitis (EAE), IDDM, scleroderma, and uveitis in animal models and assessment of genetic, immunological, and biochemical parameters underlying spontaneous or exogenous antigen-induced diseases. Written in the highly successful "Methods in Molecular Biology(tm)" series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory.

Through and intuitive, "Autoimmunity: Methods and Protocols, Second Edition" seeks to aid scientists in the autoimmunity field to extract new meaning of old models and developing new ones."

This book's aim is to study the mathematical and computational models to analyze the progress, prognosis, prevention, and panacea of breast cancer. The book discusses application of Markov chains and transient mappings, Charlie-Simpson numerical algorithm, models represented by nonlinear reaction-diffusion-type partial differential equations, and related techniques. The book also attempts to design mathematical model of targeted strategic treatments by using Skilled Killer Drugs (SKD1 and SKD2) to suggest the improvisation of future cancer treatments. Both graduate students and researchers of computational biology and oncologists will benefit by studying this book. Researchers of cancer studies and biological sciences will also find this work helpful.

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.

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 fourth volume of a continuing series.

Hemoglobin defects, specifically sickle cell disease & thalassemia, combined, constitute the most common monogenic disorders in the world. In fact, nearly 2% of the world's population carries a globin gene mutation. The transfer of the corrective globin gene through the HSC compartment by allogeneic HSC transplantation (HSCT) has already proven curative in both SCD and thalassemia patients, and provides the proof of concept that genetic manipulation of the defective organ might be equally therapeutic. However, procedural toxicities and the requirement of an HLA-matched sibling donor limit this approach to a fraction of affected individuals. The editors review the progress & the state of the field in HSCT for hemoglobinopathies & shed light on the major changes expected in the next decade. Although allogeneic HSCT is a curative option, it is limited by the availability of matched donors, which are often available only to 15-20% of patients. An alternative to allogeneic HS CT is genetic correction of autologous HSCs, to overcome donor availability & immune side effects. This Book reviews the progress made on additive gene therapy approaches & the current state of the field. Finally, targeted genetic correction is emerging as a novel therapeutic strategy in the hemoglobinopathies. Although ideal, the inefficiency of targeted correction was rate limiting for translation of this technology to the clinic. With advancements in zinc finger nucleases and TALE endonuclease mediated targeted correction, correction frequencies in hematopoietic stem cells is now reaching levels that may become clinically relevant. Furthermore, the ability to generate autologous embryonic stem cell like cells from primary somatic cells (skin fibroblasts or hematopoietic cells) of the affected individual has allowed for the potential application of genetic correction strategies.This Book reviews upcoming genetic strategies to reactivate fetal hemoglobin production and research advances.

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 third volume of a continuing series.

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.