Abstract
There is now conclusive evidence that gene therapy can lead to real clinical benefit. Initial enthusiasm has been muted by set-backs related to viral vectors including retroviral oncogenesis and adenoviral inflammatory response. Plasmid- mediated muscle-targeted gene transfer offers the potential of a cost-effective pharmaceutical grade therapy delivered by simple intramuscular injection without the need for anaesthetic, cell culture, transplantation or immunosuppression. This approach is particularly appropriate for long-term circulating therapeutic protein replacement currently requiring repeated injection therapy. Wide-ranging clinical applications include haemophilia, chronic anaemia, growth hormone deficiency and diabetes. Inadequate transgene expression, unregulated protein delivery and immune response have been major limiting factors. Recent innovations including in situ electroporation enabling sustained systemic protein delivery within the therapeutic range are reviewed. Pharmacological and physiological approaches to regulation are discussed in addition to the role of innate and humoral immunity. Translation of advances in all of these areas to clinical success will enable muscle-targeted gene therapy to capitalise on its inherent strengths and realise its long-standing promise.
Keywords: Diabetes, erythropoietin, haemophilia, furin, electroporation, lipoplex, transcriptional regulation, CpG
Current Gene Therapy
Title: Plasmid-Mediated Muscle-Targeted Gene Therapy for Circulating Therapeutic Protein Replacement: A Tale of the Tortoise and the Hare?
Volume: 6 Issue: 1
Author(s): Jarupa Ratanamart and James A.M. Shaw
Affiliation:
Keywords: Diabetes, erythropoietin, haemophilia, furin, electroporation, lipoplex, transcriptional regulation, CpG
Abstract: There is now conclusive evidence that gene therapy can lead to real clinical benefit. Initial enthusiasm has been muted by set-backs related to viral vectors including retroviral oncogenesis and adenoviral inflammatory response. Plasmid- mediated muscle-targeted gene transfer offers the potential of a cost-effective pharmaceutical grade therapy delivered by simple intramuscular injection without the need for anaesthetic, cell culture, transplantation or immunosuppression. This approach is particularly appropriate for long-term circulating therapeutic protein replacement currently requiring repeated injection therapy. Wide-ranging clinical applications include haemophilia, chronic anaemia, growth hormone deficiency and diabetes. Inadequate transgene expression, unregulated protein delivery and immune response have been major limiting factors. Recent innovations including in situ electroporation enabling sustained systemic protein delivery within the therapeutic range are reviewed. Pharmacological and physiological approaches to regulation are discussed in addition to the role of innate and humoral immunity. Translation of advances in all of these areas to clinical success will enable muscle-targeted gene therapy to capitalise on its inherent strengths and realise its long-standing promise.
Export Options
About this article
Cite this article as:
Ratanamart Jarupa and Shaw A.M. James, Plasmid-Mediated Muscle-Targeted Gene Therapy for Circulating Therapeutic Protein Replacement: A Tale of the Tortoise and the Hare?, Current Gene Therapy 2006; 6 (1) . https://dx.doi.org/10.2174/156652306775515583
DOI https://dx.doi.org/10.2174/156652306775515583 |
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
-
Chromatin Remodeling Agents for Cancer Therapy
Reviews on Recent Clinical Trials Immunotherapeutic and Immunoregulatory Drugs in Haematologic Malignancies
Current Topics in Medicinal Chemistry Histone Lysine-Specific Methyltransferases and Demethylases in Carcinogenesis: New Targets for Cancer Therapy and Prevention
Current Cancer Drug Targets The Tachykinergic System as Avenues for Drug Intervention
Recent Patents on CNS Drug Discovery (Discontinued) Modelling and Measuring Redox Cycling and Cytotoxicity of Quinones
Drug Metabolism Letters Targeting Bcl-2 in CLL
Current Medicinal Chemistry Biodegradable Nanoparticles: A Recent Approach and Applications
Current Drug Targets Mechanisms of Resistance to Photodynamic Therapy
Current Medicinal Chemistry DNA Topoisomerase II Enzymes as Molecular Targets for Cancer Chemotherapy
Current Cancer Drug Targets Artificial Intelligence, Big Data and Machine Learning Approaches in Precision Medicine & Drug Discovery
Current Drug Targets MicroRNAs and Cancer; an Overview
Current Pharmaceutical Biotechnology Irinotecan for Treatment of Childhood Cancers: A Promising Therapeutic Partner
Current Cancer Therapy Reviews Polyphenols: Biological Activities, Molecular Targets, and the Effect of Methylation
Current Molecular Pharmacology Advances in DNA-Ligands with Groove Binding, Intercalating and/or Alkylating Activity: Chemistry, DNA-Binding and Biology
Current Medicinal Chemistry Nanoparticles for Tumor Targeted Therapies and Their Pharmacokinetics
Current Drug Metabolism Evaluation of Polygonum bistorta for Anticancer Potential Using Selected Cancer Cell Lines
Medicinal Chemistry E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets
Current Cancer Drug Targets Induction and Escalation Therapies in Multiple Sclerosis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy
Current Drug Delivery Iron Chelating Strategies in Systemic Metal Overload, Neurodegeneration and Cancer
Current Medicinal Chemistry