Abstract
Since the early days of gene therapy, muscle has been one the most studied tissue targets for the correction of enzyme deficiencies and myopathies. Several preclinical and clinical studies have been conducted using adeno-associated virus (AAV) vectors. Exciting progress has been made in the gene delivery technologies, from the identification of novel AAV serotypes to the development of novel vector delivery techniques. In parallel, significant knowledge has been generated on the host immune system and its interaction with both the vector and the transgene at the muscle level. In particular, the role of underlying muscle inflammation, characteristic of several diseases affecting the muscle, has been defined in terms of its potential detrimental impact on gene transfer with AAV vectors. At the same time, feedback immunomodulatory mechanisms peculiar of skeletal muscle involving resident regulatory T cells have been identified, which seem to play an important role in maintaining, at least to some extent, muscle homeostasis during inflammation and regenerative processes. Devising strategies to tip this balance towards unresponsiveness may represent an avenue to improve the safety and efficacy of muscle gene transfer with AAV vectors.
Keywords: AAV vectors, Muscle, Clinical trials, Immune responses, Tolerance.
Current Gene Therapy
Title:The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer
Volume: 15 Issue: 4
Author(s): Florence Boisgerault and Federico Mingozzi
Affiliation:
Keywords: AAV vectors, Muscle, Clinical trials, Immune responses, Tolerance.
Abstract: Since the early days of gene therapy, muscle has been one the most studied tissue targets for the correction of enzyme deficiencies and myopathies. Several preclinical and clinical studies have been conducted using adeno-associated virus (AAV) vectors. Exciting progress has been made in the gene delivery technologies, from the identification of novel AAV serotypes to the development of novel vector delivery techniques. In parallel, significant knowledge has been generated on the host immune system and its interaction with both the vector and the transgene at the muscle level. In particular, the role of underlying muscle inflammation, characteristic of several diseases affecting the muscle, has been defined in terms of its potential detrimental impact on gene transfer with AAV vectors. At the same time, feedback immunomodulatory mechanisms peculiar of skeletal muscle involving resident regulatory T cells have been identified, which seem to play an important role in maintaining, at least to some extent, muscle homeostasis during inflammation and regenerative processes. Devising strategies to tip this balance towards unresponsiveness may represent an avenue to improve the safety and efficacy of muscle gene transfer with AAV vectors.
Export Options
About this article
Cite this article as:
Boisgerault Florence and Mingozzi Federico, The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer, Current Gene Therapy 2015; 15 (4) . https://dx.doi.org/10.2174/1566523215666150630121750
DOI https://dx.doi.org/10.2174/1566523215666150630121750 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Genetics and Epigenetics Mechanism in the Pathogenesis of Behçet’s Disease
Current Rheumatology Reviews Berberine Inhibits the Gene Expression and Production of Proinflammatory Cytokines by Mononuclear Cells in Rheumatoid Arthritis and Healthy Individuals
Current Rheumatology Reviews Role of Positron Emission Tomography for Central Nervous System Involvement in Systemic Autoimmune Diseases: Status and Perspectives
Current Medicinal Chemistry Anti-Inflammatory Drugs and Statins for Arterial Stiffness Reduction
Current Pharmaceutical Design Molecular Mechanisms of Diabetic Nephropathy and Its Therapeutic Intervention
Current Drug Targets Histopathology of Connective Tissue Disease-Associated Pleuropulmonary Disease
Current Respiratory Medicine Reviews Choice of Biologic Therapy for Patients with Rheumatoid Arthritis: The Infection Perspective
Current Rheumatology Reviews Influence of Leptin on Immunity
Current Immunology Reviews (Discontinued) Cell to Cell Spreading of Misfolded Proteins as a Therapeutic Target in Motor Neuron Disease
Current Medicinal Chemistry Mixed Connective Tissue Disease, a Roundabout to Rheumatic Diseases?
Current Rheumatology Reviews Autoimmune Diseases and Atherosclerosis: The Inflammatory Connection
Current Immunology Reviews (Discontinued) Update on Intravenous Immunoglobulins (IVIg) Mechanisms of Action and Off- Label use in Autoimmune Diseases
Current Pharmaceutical Design Cardiovascular Complications of HIV Infection and Treatment
Cardiovascular & Hematological Agents in Medicinal Chemistry Allopurinol Hypersensitivity Reactions: Desensitization Strategies and New Therapeutic Alternative Molecules
Inflammation & Allergy - Drug Targets (Discontinued) Various Non-Injectable Delivery Systems for the Treatment of Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Evidence for Altered LRP/RAGE Expression in Alzheimer Lesion Pathogenesis
Current Alzheimer Research Identification of Target Antigens of Antiendothelial Cell Antibodies Against Human Brain Microvascular Endothelial Cells in Healthy Subjects
Current Neurovascular Research Preface
Current Rheumatology Reviews Secondary Hypertension: The Ways of Management
Current Vascular Pharmacology Role of Oxidized Phospholipids in Acute Lung Injury
Current Respiratory Medicine Reviews