Abstract
The search for methods to control physiological levels of carbon monoxide (CO), a vasoactive molecule, and bilibrubin, an antioxidant, have improved our understanding of the protective role of heme oxygenase (HO) against oxidative injury. HO activity can assist other antioxidant systems in diminishing the overall production of reactive oxygen species, thus contributing to cellular resistance to such injury. Overexpression of HO gene by targeted gene transfer has become a powerful tool for studying the role of this human enzyme. Successful and functional HO gene transfer requires two essential elements. First, the HO gene must be delivered into a safe vector, such as the adenoviral, retroviral and leptosome based vectors that are currently being used in clinical trials. The use of non-viral vectors has also been described. Second, with the exception of HO gene delivery to ocular or cardiovascular tissue via catheter-based interventions, HO gene delivery must be site and organ specific. Site-specific delivery of HO-1 to renal structures in SHR, specifically mTAL, using Na+-K+ Cl - cotransporter (NKCC2 promoter), has been shown to normalize blood pressure and provide protection to mTAL against oxidative injury, respectively. Human HO-1 gene transfer into endothelial cells has been shown to attenuate Ang II- TNF- and hememediated DNA damage. Furthermore, delivery of human HO-1 into SHR has been shown to enhance somatic body growth and cell proliferation. The ability to transfect human HO gene and to demonstrate its expression may offer a new therapeutic strategy for treating pathological conditions, such as hypertension, trauma and hemorrhage.
Keywords: retroviral, adenoviral, hypertension, hemorrhage, vascular disease, carbon monoxide, cell proliferation
Current Pharmaceutical Design
Title: Therapeutic Applications of Human Heme Oxygenase Gene Transfer and Gene Therapy
Volume: 9 Issue: 30
Author(s): Nader G. Abraham
Affiliation:
Keywords: retroviral, adenoviral, hypertension, hemorrhage, vascular disease, carbon monoxide, cell proliferation
Abstract: The search for methods to control physiological levels of carbon monoxide (CO), a vasoactive molecule, and bilibrubin, an antioxidant, have improved our understanding of the protective role of heme oxygenase (HO) against oxidative injury. HO activity can assist other antioxidant systems in diminishing the overall production of reactive oxygen species, thus contributing to cellular resistance to such injury. Overexpression of HO gene by targeted gene transfer has become a powerful tool for studying the role of this human enzyme. Successful and functional HO gene transfer requires two essential elements. First, the HO gene must be delivered into a safe vector, such as the adenoviral, retroviral and leptosome based vectors that are currently being used in clinical trials. The use of non-viral vectors has also been described. Second, with the exception of HO gene delivery to ocular or cardiovascular tissue via catheter-based interventions, HO gene delivery must be site and organ specific. Site-specific delivery of HO-1 to renal structures in SHR, specifically mTAL, using Na+-K+ Cl - cotransporter (NKCC2 promoter), has been shown to normalize blood pressure and provide protection to mTAL against oxidative injury, respectively. Human HO-1 gene transfer into endothelial cells has been shown to attenuate Ang II- TNF- and hememediated DNA damage. Furthermore, delivery of human HO-1 into SHR has been shown to enhance somatic body growth and cell proliferation. The ability to transfect human HO gene and to demonstrate its expression may offer a new therapeutic strategy for treating pathological conditions, such as hypertension, trauma and hemorrhage.
Export Options
About this article
Cite this article as:
Abraham G. Nader, Therapeutic Applications of Human Heme Oxygenase Gene Transfer and Gene Therapy, Current Pharmaceutical Design 2003; 9 (30) . https://dx.doi.org/10.2174/1381612033453758
DOI https://dx.doi.org/10.2174/1381612033453758 |
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
-
Targeting Tumor Angiogenesis in Gastrointestinal Malignancies
Current Angiogenesis (Discontinued) Role of NFAT5 in Inflammatory Disorders Associated with Osmotic Stress
Current Genomics Nitric Oxide as a Marker for Levo-Thyroxine Therapy in Subclinical Hypothyroid Patients
Current Vascular Pharmacology Anti-Inflammatory Actions of the Heme Oxygenase-1 Pathway
Current Pharmaceutical Design Gestational Diabetes and the Metabolic Syndrome: Can Obesity and Small, Dense Low Density Lipoproteins be Key Mediators of this Association?
Current Pharmaceutical Biotechnology Editorial: [Hot Topic: Nanotechnology and Patents in Agriculture, Food Technology, Nutrition and Medicine - Advantages and Risks]
Recent Patents on Food, Nutrition & Agriculture Novel Antidepressant Drugs, Arterial Hypertension and Cardiovascular Disease
Recent Patents on Cardiovascular Drug Discovery Serum Uric Acid and Progression of Autosomal Dominant Polycystic Kidney Disease: Results from the HALT PKD Trials
Current Hypertension Reviews Renin-Angiotensin-Aldosterone System in Autosomal Dominant Polycystic Kidney Disease
Current Hypertension Reviews Mineralocorticoid Antagonists in ESRD: An Overview of Clinical Trial Evidence
Current Vascular Pharmacology Clinical Pharmacology of Novel Anti-Alzheimer Disease Modifying Medications
Current Topics in Medicinal Chemistry Mesenchymal Stem Cell-derived Extracellular Vesicles for Renal Repair
Current Gene Therapy Fermented Foods: Patented Approaches and Formulations for Nutritional Supplementation and Health Promotion
Recent Patents on Food, Nutrition & Agriculture Atherogenesis in Renal Patients: A Model of Vascular Disease?
Current Vascular Pharmacology Targeting the Histamine H4 Receptor: Future Drugs for Inflammatory Diseases
Current Organic Chemistry Pannexin Channels: The Emerging Therapeutic Targets
Current Drug Targets Mental Health Problems Experienced by Patients with Rheumatic Diseases During COVID-19 Pandemic
Current Rheumatology Reviews Meet the Editorial Board:
Current Topics in Medicinal Chemistry Ca2+ Signalling in Damaged Endothelium: Do Connexin Hemichannels Aid in Filling the Gap?
Current Drug Therapy Pharmacological Management of No Reflow During Percutaneous Coronary Intervention
Current Vascular Pharmacology