Abstract
Hydrodynamic gene delivery to the liver has potential as a safe and effective approach for clinical liver gene therapy. However, the simplicity of the technique in rodents – an intravenous injection – belies the theoretical and practical complexity for clinical application. A key issue is that outflow obstruction of the DNA solution from the liver is a critical factor for raising intrahepatic vascular pressure, which in turn provides the force to swell the liver and effect gene delivery. For conventional hydrodynamic gene delivery via tail vein injection, this outflow obstruction is provided naturally by the vascular resistance of the gut, spleen and pancreas. For regional hydrodynamic gene delivery to the liver, outflow obstruction to create a closed system requires surgical intervention, making it unlikely that minimally invasive techniques will be possible in the clinic. Intrinsic factors, in particular compliance (elasticity) of the liver are likely to be crucial in determining the degree of swelling for a given level of intrahepatic vascular pressure. Liver compliance is likely to be the major reason for the low level of hydrodynamic gene delivery in the pig model, and will influence the effectiveness of the approach in man, both in general and in different disease states.
Keywords: Hydrodynamic gene delivery, liver, gene therapy, mechanisms, clinical application
Current Gene Therapy
Title: Hydrodynamic Gene Delivery to the Liver: Theoretical and Practical Issues for Clinical Application
Volume: 9 Issue: 2
Author(s): Greta J. Sawyer, Mohamed Rela, Mark Davenport, Michael Whitehorne, Xiaohong Zhang and John W. Fabre
Affiliation:
Keywords: Hydrodynamic gene delivery, liver, gene therapy, mechanisms, clinical application
Abstract: Hydrodynamic gene delivery to the liver has potential as a safe and effective approach for clinical liver gene therapy. However, the simplicity of the technique in rodents – an intravenous injection – belies the theoretical and practical complexity for clinical application. A key issue is that outflow obstruction of the DNA solution from the liver is a critical factor for raising intrahepatic vascular pressure, which in turn provides the force to swell the liver and effect gene delivery. For conventional hydrodynamic gene delivery via tail vein injection, this outflow obstruction is provided naturally by the vascular resistance of the gut, spleen and pancreas. For regional hydrodynamic gene delivery to the liver, outflow obstruction to create a closed system requires surgical intervention, making it unlikely that minimally invasive techniques will be possible in the clinic. Intrinsic factors, in particular compliance (elasticity) of the liver are likely to be crucial in determining the degree of swelling for a given level of intrahepatic vascular pressure. Liver compliance is likely to be the major reason for the low level of hydrodynamic gene delivery in the pig model, and will influence the effectiveness of the approach in man, both in general and in different disease states.
Export Options
About this article
Cite this article as:
Sawyer J. Greta, Rela Mohamed, Davenport Mark, Whitehorne Michael, Zhang Xiaohong and Fabre W. John, Hydrodynamic Gene Delivery to the Liver: Theoretical and Practical Issues for Clinical Application, Current Gene Therapy 2009; 9 (2) . https://dx.doi.org/10.2174/156652309787909535
DOI https://dx.doi.org/10.2174/156652309787909535 |
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
-
Structure-Function Relationships of Iodinated Contrast Media and Risk of Nephrotoxicity
Current Medicinal Chemistry Three Dimensional Echocardiography: Recent Trends in Segmen tation Methods
Current Medical Imaging Roles of Insulin Resistance, Endothelial Dysfunction and Lifestyle Changes in the Development of Cardiovascular Disease in Diabetic Patients
Current Drug Targets Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension
Current Pharmaceutical Design Obesity and Heart Failure
Endocrine, Metabolic & Immune Disorders - Drug Targets Quantifying Glomerular Filtration Rates: Kidney Function Analysis Method and Apparatus
Recent Patents on Biomarkers Generation of Human Cardiomyocytes for Cardiac Regenerative Therapies: Differentiation and Direct Reprogramming
Current Pharmaceutical Design Pharmacological Regulation of Dyslipoproteinaemia in Insulin Resistant States
Current Vascular Pharmacology Targeting Gender Difference in the Introduction of New Drugs for Diabetes Mellitus and Metabolic Disorders
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Pharmacological Therapy in Children with Atrial Fibrillation and Atrial Flutter
Current Pharmaceutical Design Limitations and Potential Clinical Application on Contrast Echocardiography
Current Cardiology Reviews The Modulating Effects of Endogenous Substances on Drug Metabolising Enzymes and Implications for Inter-Individual Variability and Quantitative Prediction
Current Drug Metabolism Cellular Mechanisms of Brain Injury and Cell Death
Current Pharmaceutical Design Clinical PET Imaging of Insulinoma and Beta-Cell Hyperplasia
Current Pharmaceutical Design Role of Ca2+-Sensitive K+ Currents in Controlling Ventricular Repolarization: Possible Implications for Future Antiarrhytmic Drug Therapy
Current Medicinal Chemistry Gesture Interaction for Coronary Heart Diseases Based on Wavelet Transform and Semi-Continuous Hidden Markov Model in Augmented Reality
Recent Advances in Electrical & Electronic Engineering Recent Advances in Exercise Testing
Current Cardiology Reviews A Disposable, Highly Sensitive Biosensing System: Determination of Haptoglobin as a Significant Acute Phase Biomarker
Current Analytical Chemistry In Vivo Measurement in Pigs of Wash-In Kinetics of Xenon at its Site of Action
Current Clinical Pharmacology Pharmacological manipulation of peripheral vascular resistance in special clinical situations after pediatric cardiac surgery
Current Vascular Pharmacology