Abstract
Autoimmune diseases frequently develop as a result of an abnormal activation of autoreactive T cells, excessive production of proinflammatory cytokines, particularly by CD4+ Th1 cells, and subsequent tissue destruction. Cytokine-dependent immunotherapy can be applied to alter the balance between Th1 and Th2 cell activity, or proinflammatory versus immunosuppressive cytokine profiles. Cytotoxic T lymphocyte (CTL) and / or macrophage activity can also be suppressed. Gene transfer offers numerous advantages for the in vivo delivery of cytokines or their receptors for immunotherapeutic use. We have relied on the injection of naked plasmid DNA into skeletal muscle to deliver therapeutic genes. In particular, we have successfully used this approach to deliver neutralizing cytokine receptors such as interferon γ (IFNγ)-receptor-Ig fusion proteins or anti-inflammatory cytokines such as transforming growth factor β-1 (TGF-β1) and interleukin 4 (IL-4). Intramuscular gene therapy is effective in protecting against several experimental autoimmune diseases including insulin-dependent diabetes mellitus (IDDM), experimental allergic encephalomyelitis (EAE), and systemic lupus erythematosus (SLE). Another promising approach involves DNA vaccination by plasmid-based codelivery of genes encoding an autoantigen and either a cytokine or other immunomodulatory molecule. Plasmid vectors offer interesting advantages over viral vectors, since they are simple to produce, nonimmunogenic and non-pathogenic. They can be repeatedly administered with relatively prolonged periods of expression in vivo, ranging from weeks to months after each injection. Plasmid-based intramuscular gene transfer has great therapeutic potential in the areas of autoimmune and inflammatory disorders.
Keywords: Immune Modulation, Plasmid, DNA-mediated, Cytokine, Gene, systemic lupus erythematosus, autoimmune
Current Pharmaceutical Design
Title: Immune Modulation by Plasmid DNA-mediated Cytokine Gene Transfer
Volume: 9 Issue: 1
Author(s): Ciriaco A. Piccirillo and Gerald J. Prud'homme
Affiliation:
Keywords: Immune Modulation, Plasmid, DNA-mediated, Cytokine, Gene, systemic lupus erythematosus, autoimmune
Abstract: Autoimmune diseases frequently develop as a result of an abnormal activation of autoreactive T cells, excessive production of proinflammatory cytokines, particularly by CD4+ Th1 cells, and subsequent tissue destruction. Cytokine-dependent immunotherapy can be applied to alter the balance between Th1 and Th2 cell activity, or proinflammatory versus immunosuppressive cytokine profiles. Cytotoxic T lymphocyte (CTL) and / or macrophage activity can also be suppressed. Gene transfer offers numerous advantages for the in vivo delivery of cytokines or their receptors for immunotherapeutic use. We have relied on the injection of naked plasmid DNA into skeletal muscle to deliver therapeutic genes. In particular, we have successfully used this approach to deliver neutralizing cytokine receptors such as interferon γ (IFNγ)-receptor-Ig fusion proteins or anti-inflammatory cytokines such as transforming growth factor β-1 (TGF-β1) and interleukin 4 (IL-4). Intramuscular gene therapy is effective in protecting against several experimental autoimmune diseases including insulin-dependent diabetes mellitus (IDDM), experimental allergic encephalomyelitis (EAE), and systemic lupus erythematosus (SLE). Another promising approach involves DNA vaccination by plasmid-based codelivery of genes encoding an autoantigen and either a cytokine or other immunomodulatory molecule. Plasmid vectors offer interesting advantages over viral vectors, since they are simple to produce, nonimmunogenic and non-pathogenic. They can be repeatedly administered with relatively prolonged periods of expression in vivo, ranging from weeks to months after each injection. Plasmid-based intramuscular gene transfer has great therapeutic potential in the areas of autoimmune and inflammatory disorders.
Export Options
About this article
Cite this article as:
Piccirillo A. Ciriaco and Prud'homme J. Gerald, Immune Modulation by Plasmid DNA-mediated Cytokine Gene Transfer, Current Pharmaceutical Design 2003; 9 (1) . https://dx.doi.org/10.2174/1381612033392404
DOI https://dx.doi.org/10.2174/1381612033392404 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Monoamine Involvement in the Antidepressant-Like Effect of β-Caryophyllene
CNS & Neurological Disorders - Drug Targets Voltage-Gated Sodium Channel Blockers as Immunomodulators
Recent Patents on CNS Drug Discovery (Discontinued) Gene Therapy and Biologic Therapy with Interleukin?4
Current Gene Therapy Autoantibodies in Autoimmune Diseases
Current Pharmaceutical Design Therapeutic Strategies in Parkinsons Disease
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Protein Tyrosine Nitration: Role in Aging
Current Aging Science Immune System Induction of Nerve Growth Factor in an Animal Model of Multiple Sclerosis: Implications in Re-Myelination and Myelin RepairATION AND MYELIN REPAIR
CNS & Neurological Disorders - Drug Targets In Vitro and In Vivo Models of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Solving the Blood-Brain Barrier Challenge for the Effective Treatment of HIV Replication in the Central Nervous System
Current Pharmaceutical Design Mucopolysaccharidosis Type III (Sanfilippo Syndrome): Emerging Treatment Strategies
Current Pharmaceutical Biotechnology Programmed Symptoms: Disparate Effects United by Purpose
Current Rheumatology Reviews The Renin-Angiotensin System and the Neurodegenerative Diseases: A Brief Review
Protein & Peptide Letters New Actors for the Immunological Mechanisms Involved in the Materno- Fetal Tolerance
Current Women`s Health Reviews Stem Cell-Based Immunomodulation in Type 1 Diabetes: Beyond the Regenerative Approach
Current Pharmaceutical Design Protein Glycation: An Old Villain is Shedding Secrets
Combinatorial Chemistry & High Throughput Screening Functional Characteristic of Snake Venom Disintegrins: Potential Therapeutic Implication
Current Pharmaceutical Design Involvement of the Blood-Brain Barrier in Metabolic Regulation
CNS & Neurological Disorders - Drug Targets Application of Mesenchymal Stem Cells in Melanoma: A Potential Therapeutic Strategy for Delivery of Targeted Agents
Current Medicinal Chemistry Antiviral Activity of Jodantipyrin – An Anti-Inflammatory Oral Therapeutic with Interferon-Inducing Properties
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Knockdown of C-C Chemokine Receptor 5 (CCR5) is Protective Against Cerebral Ischemia and Reperfusion Injury
Current Neurovascular Research