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
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...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
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
![](/images/wayfinder.jpg)
- 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
-
Effects of Cyclosporine A and Itraconazole on Permeability, Biliary Excretion and Pharmacokinetics of Amlidipine
Drug Metabolism Letters Role of ARBs in the Blood Hypertension Therapy and Prevention of Cardiovascular Events
Current Drug Targets Therapeutic Potential of Drugs Targeting Pathophysiology of Intracerebral Hemorrhage: From Animal Models to Clinical Applications
Current Pharmaceutical Design Effects of a Hypocaloric Diet on Obesity Biomarkers: Prevention of Low-Grade Inflammation since Childhood
Current Pharmaceutical Design Diabetic Cardiomyopathy and its Prevention by Metallothionein: Experimental Evidence, Possible Mechanisms and Clinical Implications
Current Medicinal Chemistry Is the Cytoskeleton an Intracellular Receptor for Adrenomedullin and PAMP?
Current Protein & Peptide Science Scorpion Toxin Polyptides as Therapeutic Agents: An Overview
Protein & Peptide Letters Identification of Canonical Transient Receptor Potential (TRPC) Channel Proteins in Native Vascular Smooth Muscle Cells
Current Medicinal Chemistry Why and How We Should Treat Elderly Patients with Hypertension?
Current Vascular Pharmacology Detecting the Association Between Residual Thrombus and Post-thrombotic Classification of Chronic Venous Disease with Range Regression
Reviews on Recent Clinical Trials Endothelial Dysfunction and Inflammation in Ischemic Stroke Pathogenesis
Current Pharmaceutical Design Hepatocyte Growth Factor Attenuates the Development of TGF-β1- Induced EndMT through Down-regulating the Notch Signaling
Endocrine, Metabolic & Immune Disorders - Drug Targets Silent Partner in Blood Vessel Homeostasis? Pervasive Role of Nitric Oxide in Vascular Disease
Current Hypertension Reviews Novel Therapeutic Targets for Phosphodiesterase 5 Inhibitors: current state-of-the-art on systemic arterial hypertension and atherosclerosis
Current Pharmaceutical Biotechnology Recent Advances in Bioactive Peptides as Functional Food for Health Promotions and Medicinal Applications
Protein & Peptide Letters EPC Dysfunction and Immune Networks: Translating Opportunities for Clinical Setting in Personalized Medicine
Current Medicinal Chemistry Synthesis and Biological Activity of 3-(2, 8, 9-Trioxa-aza-1-germatricyclo [3. 3. 3. 0]undecane-1-yl)-hydroxycinnamic Acids
Medicinal Chemistry High Fat Diet-Induced Obesity Stimulate Depressive Behavior in Rats
Current Psychopharmacology Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer’s Disease Patients?
CNS & Neurological Disorders - Drug Targets Potential Anti-cancer Drugs Commonly Used for Other Indications
Current Cancer Drug Targets