Abstract
Despite the unprecedented beneficial effects of rAAV gene therapy in animal models of Duchenne muscular dystrophy (DMD), the need to inject large amounts of vector in vivo to improve phenotype raises obvious biosafety concerns. While rAAV vectors generally exhibit a good safety profile, specific pathological phenotypes such as those observed in dystrophin-deficient muscles may promote immunotoxic/genotoxic effects. Increasing the therapeutic index of rAAV in DMD muscles by reducing the effective dose could be a pivotal means of ensuring efficient clinical translation. This requires a comprehensive understanding of the rAAV transduction process, which is almost always studied in non-pathological tissues or in vitro. In this review, we focus on the molecular fate of rAAV after injection, and how the individual stages of transduction could be affected in the context of DMD.
Keywords: Muscle, Duchenne muscular dystrophy, Adeno-associated virus, Gene therapy, Restriction factors, In vivo.
Current Gene Therapy
Title:Restriction Factors Against Recombinant Adeno-associated Virus Vectormediated Gene Transfer in Dystrophin-deficient Muscles
Volume: 16 Issue: 3
Author(s): Jean-Baptiste Dupont
Affiliation:
Keywords: Muscle, Duchenne muscular dystrophy, Adeno-associated virus, Gene therapy, Restriction factors, In vivo.
Abstract: Despite the unprecedented beneficial effects of rAAV gene therapy in animal models of Duchenne muscular dystrophy (DMD), the need to inject large amounts of vector in vivo to improve phenotype raises obvious biosafety concerns. While rAAV vectors generally exhibit a good safety profile, specific pathological phenotypes such as those observed in dystrophin-deficient muscles may promote immunotoxic/genotoxic effects. Increasing the therapeutic index of rAAV in DMD muscles by reducing the effective dose could be a pivotal means of ensuring efficient clinical translation. This requires a comprehensive understanding of the rAAV transduction process, which is almost always studied in non-pathological tissues or in vitro. In this review, we focus on the molecular fate of rAAV after injection, and how the individual stages of transduction could be affected in the context of DMD.
Export Options
About this article
Cite this article as:
Dupont Jean-Baptiste, Restriction Factors Against Recombinant Adeno-associated Virus Vectormediated Gene Transfer in Dystrophin-deficient Muscles, Current Gene Therapy 2016; 16 (3) . https://dx.doi.org/10.2174/1566523216666160428104325
DOI https://dx.doi.org/10.2174/1566523216666160428104325 |
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
-
Molecular Imaging: Its Application In Cardiovascular Diagnosis
Current Pharmaceutical Design Role of miRNAs in Muscle Stem Cell Biology: Proliferation, Differentiation and Death
Current Pharmaceutical Design Ranolazine and its Antiarrhythmic Actions
Cardiovascular & Hematological Agents in Medicinal Chemistry Cell Therapy for Myocardial Regeneration
Current Molecular Medicine Potential Roles of MyomiRs in Cardiac Development and Related Diseases
Current Cardiology Reviews Autoantibodies for Cardiac Channels and Sudden Cardiac Death and its Relationship to Autoimmune Disorders
Current Cardiology Reviews Stroke in Women - Oral Contraception, Pregnancy, and Hormone Replacement Therapy
Current Vascular Pharmacology Pharmacotherapy of Aortic Stenosis-Success or Failure?
Current Pharmaceutical Biotechnology Role of Coronary Microvascular Endothelial Dysfunction in the Development of Heart Failure
Current Cardiology Reviews Proteomics Analysis Revealed an Altered Left Ventricle Protein Profile in a Mouse Model of Transverse Aortic Constriction
Protein & Peptide Letters Development of Aldose Reductase Inhibitors for the Treatment of Inflammatory Disorders and Cancer: Current Drug Design Strategies and Future Directions
Current Medicinal Chemistry Targeting Potassium Channels: New Advances in Cardiovascular Therapy
Recent Patents on Cardiovascular Drug Discovery Common Genetic Conditions of Ischemic Stroke to Keep in Mind
Current Molecular Medicine Insights into the Role of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Health and Disease
Current Chemical Biology Eisenmenger Syndrome: Recent Advances in Pharmacotherapy
Cardiovascular & Hematological Agents in Medicinal Chemistry Parvovirus B19 (B19V) Infection and Pregnancy
Current Pediatric Reviews Diagnosis and Management of Heart Failure with Preserved Ejection Fraction: 10 Key Lessons
Current Cardiology Reviews Pregnancy in Type 2 Diabetes Mellitus - Problems & Promises
Current Diabetes Reviews Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy
Current Pharmaceutical Design Role of Cardiolipin in Mitochondrial Diseases and Apoptosis
Current Medicinal Chemistry