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Author: Federico Mingozzi
Publisher: Frontiers Media SA
ISBN: 2889195007
Category : Immunologic diseases. Allergy
Languages : en
Pages : 97
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Book Description
The recent wave of clinical studies demonstrating long-term therapeutic efficacy highlights the enormous potential of gene therapy as an approach to the treatment of inherited disorders and cancer. While in recent years lentiviral vectors have dominated the field of ex vivo gene therapy in man, adeno-associated virus (AAV) vectors have become the platform of choice for the in vivo gene delivery, both local and systemic. Despite the achievements in the clinic however, a number of hurdles remain to be overcome in gene therapy, these include availability of scalable vector production systems, potential issues associated with insertional mutagenesis, and concerns related to immunogenicity of gene therapeutics. For AAV vectors, clinical trials showed that immunity directed against the vector could either prevent transduction of a target tissue or limit the duration of therapeutic efficacy. Initial observations in the context of a gene therapy trial for hemophilia spurred over a decade efforts by gene therapists and immunologists to understand the mechanism and identify factors that contribute to AAV’s immunogenicity, including the prevalence of B cell and T cell immunity to wild type AAV in humans and the interaction of AAV vectors with the innate and adaptive immune system. Despite a number of important contributions in particular in the more recent past, our knowledge on the immunology of gene transfer is still rudimental; this is partly due to the fact that the basic understanding of the complex balance between tolerance and immunity to an antigen, key aspect of gene transfer with AAV, keeps evolving rapidly. However, continuing work towards a better definition of the interaction of viral vectors with the immune system has led to significant advances in the knowledge of the factors influencing the outcome of gene transfer, such as the vector dose, the immune privilege of certain tissues, and the induction of tolerance to an antigen. A better understanding of the structure-function relationship of the viral capsid has boosted the development of novel immune-escape vector variants. In addition, novel immunomodulatory strategies were established to prevent or reduce anti-capsid immunity have been developed and are being tested in preclinical models and in clinical trials. Together, these advances are bringing us closer to the goal of achieving safe and sustained therapeutic gene transfer in humans. In this research topic, a collection of Original Research and Review Articles highlights critical aspects of the interaction between gene AAV vectors and the immune system, discussing how these interactions can be either detrimental or constitute an advantage, depending on the context of gene transfer, and providing tools and resources to better understand the issue of immunogenicity of AAV vectors in gene transfer.
Author: Federico Mingozzi
Publisher: Frontiers Media SA
ISBN: 2889195007
Category : Immunologic diseases. Allergy
Languages : en
Pages : 97
Get Book
Book Description
The recent wave of clinical studies demonstrating long-term therapeutic efficacy highlights the enormous potential of gene therapy as an approach to the treatment of inherited disorders and cancer. While in recent years lentiviral vectors have dominated the field of ex vivo gene therapy in man, adeno-associated virus (AAV) vectors have become the platform of choice for the in vivo gene delivery, both local and systemic. Despite the achievements in the clinic however, a number of hurdles remain to be overcome in gene therapy, these include availability of scalable vector production systems, potential issues associated with insertional mutagenesis, and concerns related to immunogenicity of gene therapeutics. For AAV vectors, clinical trials showed that immunity directed against the vector could either prevent transduction of a target tissue or limit the duration of therapeutic efficacy. Initial observations in the context of a gene therapy trial for hemophilia spurred over a decade efforts by gene therapists and immunologists to understand the mechanism and identify factors that contribute to AAV’s immunogenicity, including the prevalence of B cell and T cell immunity to wild type AAV in humans and the interaction of AAV vectors with the innate and adaptive immune system. Despite a number of important contributions in particular in the more recent past, our knowledge on the immunology of gene transfer is still rudimental; this is partly due to the fact that the basic understanding of the complex balance between tolerance and immunity to an antigen, key aspect of gene transfer with AAV, keeps evolving rapidly. However, continuing work towards a better definition of the interaction of viral vectors with the immune system has led to significant advances in the knowledge of the factors influencing the outcome of gene transfer, such as the vector dose, the immune privilege of certain tissues, and the induction of tolerance to an antigen. A better understanding of the structure-function relationship of the viral capsid has boosted the development of novel immune-escape vector variants. In addition, novel immunomodulatory strategies were established to prevent or reduce anti-capsid immunity have been developed and are being tested in preclinical models and in clinical trials. Together, these advances are bringing us closer to the goal of achieving safe and sustained therapeutic gene transfer in humans. In this research topic, a collection of Original Research and Review Articles highlights critical aspects of the interaction between gene AAV vectors and the immune system, discussing how these interactions can be either detrimental or constitute an advantage, depending on the context of gene transfer, and providing tools and resources to better understand the issue of immunogenicity of AAV vectors in gene transfer.
Author: Katherine High
Publisher: Frontiers E-books
ISBN: 2889190552
Category :
Languages : en
Pages : 96
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Book Description
Viral vectors are superior tools for gene therapy and as a genetic vaccine platform because viruses have evolved to efficiently infect and transfer their genomes to cells. Several impressive successes in viral vector-based gene therapies have been reported in humans, including restoration of vision in patients with Leber’s congenital amaurosis by retinal gene transfer and cures for severe immune deficiencies by gene transfer to hematopoietic stem cells. However, the mammalian immune system has evolved in parallel to fend off invading pathogens such as viruses. Innate and antigen-specific adaptive immune responses against viral vectors and therapeutic transgene products pose serious hurdles for successful gene therapy. Pre-existing immunity in humans, resulting from prior exposure to the parent virus that forms the basis for the gene transfer vehicle may be derived from, often prevents efficient gene transfer. This problem also reduces our ability to use certain vectors for genetic vaccination or in anti-cancer therapy. For these reasons, the gene transfer community has been extensively studying the mechanisms of immune responses against viral vectors and has started to develop strategies and protocols to block or circumvent such responses. Choice, design and engineering of a vector as well as the route of administration/target tissue can be optimized/ altered to minimize immune responses or evade pre-existing immunity. Immune suppression and modulation strategies are being developed in order to minimize inflammation, prevent antibody or T cell responses against vectors, and to promote tolerance to therapeutic gene products. Combinations of these approaches will likely facilitate clinical applications of gene therapy for many target diseases and also aid in vaccine development.
Author: Michael G. Kaplitt
Publisher: Gulf Professional Publishing
ISBN: 9780123976321
Category : Medical
Languages : en
Pages : 380
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Book Description
Few areas of biomedical research provide greater opportunities to capitalize upon the revolution in genomics and molecular biology than gene therapy. This is particularly true for the brain and nervous system, where gene transfer has become a key technology for basic research and has recently been translated to human therapy in several landmark clinical trials. Gene Therapy in the Brain: From Bench to Bedside represents the definitive volume on this subject. Edited by two pioneers of neurological gene therapy, this volume contains contributions by leaders who helped to create the field as well as those who are expanding the promise of gene therapy for the future of basic and clinical neuroscience. Drawing upon this extensive collective experience, this book provides clear and informative reviews on a variety of subjects which would be of interest to anyone who is currently using or contemplating exploring gene therapy for neurobiological applications. Basic gene transfer technologies are discussed, with particular emphases upon novel vehicles, immunological issues and the role of gene therapy in stem cells. Numerous research applications are reviewed, particularly in complex fields such as behavioral neurobiology. Several preclinical areas are also covered which are likely to translate into clinical studies in the near future, including epilepsy, pain and amyotrophic lateral sclerosis. Among the most exciting advances in recent years has been the use of neurological gene therapy in human clinical trials, including Parkinson's disease, Canavan disease and Batten disease. Finally, readers will find "insider" information on technological and regulatory issues which can often limit effective translation of even the most promising idea into clinical use. This work provides up-to-date information and key insights into those gene therapy issues which are important to both scientists and clinicians focusing upon the brain and central nervous system.
Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309495849
Category : Medical
Languages : en
Pages : 93
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Book Description
On April 23 and 24, 2019 the Forum on Neuroscience and Nervous System Disorders convened a workshop titled "Advancing Gene-Targeted Therapies for Central Nervous System Disorders" in Washington, DC. This public workshop brought together experts and key stakeholders from academia, government, industry, philanthropic foundations, and disease/patient-focused nonprofit organizations to explore approaches for advancing the development of gene-targeted therapies for central nervous system (CNS) disorders, and implications of developing these therapies. Participants explored lessons learned from both successful and unsuccessful clinical development programs; new knowledge about the genetic underpinnings of brain disorders; the current status and future potential of gene-targeted therapies for CNS disorders; challenges and potential solutions for translating preclinical findings to approved therapies; and patient and caregiver perspectives. They also discussed what will be needed to develop these therapies for common disorders such as Alzheimer's and Parkinson's disease, as well as neuropsychiatric and neurodevelopmental disorders such as schizophrenia and autism. The workshop included approaches that target both DNA and RNA, as well as gene products using viral vectors, antisense oligonucleotides, and RNA interference. This publication summarizes the presentations and discussion of the workshop.
Author: Houria Bachtarzi
Publisher: BoD – Books on Demand
ISBN: 1789857171
Category : Medical
Languages : en
Pages : 200
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Book Description
Ongoing advances in pharmaceutical biotechnology have paved the way to ground-breaking new biological therapeutic modalities, offering the possibility of a durable curative approach for a number of life-threatening diseases, for which the medical need is as yet unmet. Over the past decades, gene therapy has seen a massive transformation from a proof-of-concept approach to a clinical reality culminating in the regulatory approval of state-of-the-art products in the European Union and in the United States. This book captures some of the scientific progresses notably in gene transfer technologies and translational development of in vivo and ex vivo gene therapy interventions in the treatment of a broad range of complex and debilitating non-inherited and inherited disorders such as: human immunodeficiency virus 1 (HIV-1) infection, cancer, cystic fibrosis, hereditary retinopathies, haemophilia B, cardiac diseases, and chronic liver fibrosis.
Author: Andrew P. Tosolini
Publisher: Frontiers Media SA
ISBN: 2889454754
Category :
Languages : en
Pages : 220
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Book Description
Gene therapy is at the forefront of current techniques that aim to re-establish functional connectivity, after an insult to the brain, spinal cord or peripheral nerves. Gene therapy makes the most of the existing cellular machinery and anatomical networks to facilitate molecular changes in DNA, RNA and proteins aiming to repair these disrupted connections. For instance, gene therapy is currently being used to target genes in conditions including spinal cord injury, amyotrophic lateral sclerosis, spinal muscular atrophy, stroke and multiple sclerosis, amongst others. The various delivery routes include viral-vectors, genetically modified cellular implants, naked DNA/RNA, liposomes, Cre-Lox recombination, optogenetics and nanoparticles. In particular, gene therapy aims to restore function by augmenting the expression of neuroprotective/axonal growth-promoting neurotrophic factors (e.g., BDNF, CNTF, NGF and GDNF, etc.). Furthermore, the downstream intracellular signalling pathways after receptor activation can also be targeted (e.g., mTor, MAPK, etc.). On the other hand, gene therapy can also be used to downregulate and/or remove faulty mutated genes, such as those contributing to disease progression or that inhibit axonal regeneration (e.g., SOD-1, TDP-43, Nogo-A, MAG, OmGP, etc.). Depending on the methodology, these genes, for instance, can be silenced, removed or replaced to alleviate the underlying pathology. As such, gene therapy can transform a largely toxic and inhibitory milieu surrounding a neuronal/axonal insult into a growth-permissive environment that will ultimately aid neuronal survival and functional regeneration. Moreover, gene therapy has the capacity to target non-neuronal cells and can be even used for neuroanatomical tract tracing. Ultimately, the principal outcome of gene therapy is to functionally restore damaged neuronal and/or axonal connections irrespective of the system it is being introduced in to. This Research Topic is devoted to work using gene therapy for the both the central and/or peripheral nervous system.
Author: Moulay Mustapha Ennaji
Publisher: Academic Press
ISBN: 0128149671
Category : Science
Languages : en
Pages : 388
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Book Description
Emerging and Reemerging Viral Pathogens: Applied Virology Approaches Related to Human, Animal and Environmental Pathogens, Volume Two presents new research information on viruses and their impact on the scientific community. It provides a reference book on certain viruses in humans, animals and vegetal, along with a comprehensive discussion on interspecies interactions. The book then looks at the drug, vaccine and bioinformatical strategies that can be used against these viruses, giving the reader a clear understanding of transmission. The book's end goal is to create awareness that the appearance of newly transmissible pathogens is a global risk that requires shared/adoptable policies for prevention and control. Covers most emerging viral disease in humans, animals and plants Provides the most advanced tools and techniques in molecular virology and the modeling of viruses Creates awareness that the appearance of new transmissible pathogens is a global risk Highlights the need to adopt shared policies for the prevention and control of infectious diseases
Author: Anthony J. Hickey
Publisher: CRC Press
ISBN: 0429619561
Category : Medical
Languages : en
Pages : 784
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Book Description
This fully revised and updated third edition of Pharmaceutical Inhalation Aerosol Technology encompasses the scientific and technical foundation for the rationale, design, componentry, assembly and quality performance metrics of therapeutic inhalers in their delivery of pharmaceutical aerosols to treat symptoms or the underlying causes of disease. It focuses on the importance of pharmaceutical engineering as a foundational element of all inhaler products and their application to pulmonary drug delivery. The expanded scope considers previously unaddressed aspects of pharmaceutical inhalation aerosol technology and the patient interface by including aerosol delivery, lung deposition and clearance that are used as measures of effective dose delivery. Key Features: Provides a thoroughly revised and expanded reference with authoritative discussions on the physiologic,pharmacologic, metabolic, molecular, cellular and physicochemical factors, influencing the efficacy and utilization of pharmaceutical aerosols Emphasizes the importance of pharmaceutical engineering as a foundational element of all inhaler products and their application to pulmonary drug delivery Addresses the physics, chemistry and engineering principles while establishing disease relevance Expands the ‘technology’ focus of the original volumes to address the title more directly Offers an impressive breadth of coverage as well as an international flavour from outstanding editors and contributors
Author: Subhrangsu Chatterjee
Publisher: Springer Nature
ISBN: 9811985200
Category : Medical
Languages : en
Pages : 423
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Book Description
This book reviews the structure-function relationship of nucleic acids, their role in the pathophysiology of the diseases, and as therapeutic targets for human diseases. The chapters discuss the role of nucleic acids in inflammatory diseases, neurodegenerative diseases, and cancer. The book also describes recent advancements in nucleic acid-based therapy, the application of nucleic acids in diagnostics, in the development of nano-carriers, logic gates, and sensors. It explores the use of nucleic acids (RNA and DNA) as a unique and multifunctional platform for numerous applications, including therapeutics, diagnostics, nanodevices, and materials. It further examines the role of DNA methylation, histone modifiers and readers, chromatin remodelers, microRNAs, and other components of chromatin in the progression of cancer. The book also discusses the applications of nucleic acid as a vaccine and as a gene-editing tool. It also provides an overview of the clinical trials using genome editing platforms for disease treatment and the challenges in implementing the editing technology. Finally, the book elucidates a representative description of challenges associated with nucleic acid-mediated therapy.
Author: Jeffrey L. Noebels
Publisher: OUP USA
ISBN: 0199746540
Category : Medical
Languages : en
Pages : 1258
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Book Description
Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.
