Abstract
The liver is a preferred target organ for gene therapy not only for liver-specific diseases but also for disorders that require systemic delivery of a protein. Diseases that could benefit from hepatic gene transfer include hemophilia, metabolic disorders, lysosomal storage disorders, and others. For a successful delivery of the transgene and sustained expression, the protocol must avoid immune responses in order to be efficacious. A growing number of studies have demonstrated that liver-directed transfer can induce transgene product-specific immune tolerance. Tolerance obtained via this route requires optimal engineering of the vector to eliminate transgene expression in antigen presenting cells while restricting high levels of therapeutic expression to hepatocytes. Innate immune responses may prevent tolerance induction, cause toxicity, and have to be minimized. Discussed in our review is the crucial role of CD4+CD25+ regulatory T cells in tolerance to the hepatocyte-derived gene product, the immunobiology of the liver and our current understanding of its tolerogenic properties, current and proposed research as to the mechanisms behind the livers unique cellular environment, as well as development of the tools for tolerance induction such as advanced vector systems.
Current Gene Therapy
Title: Hepatic Gene Transfer as a Means of Tolerance Induction to Transgene Products
Volume: 9 Issue: 2
Author(s): Paul A. LoDuca, Brad E. Hoffman and Roland W. Herzog
Affiliation:
Abstract: The liver is a preferred target organ for gene therapy not only for liver-specific diseases but also for disorders that require systemic delivery of a protein. Diseases that could benefit from hepatic gene transfer include hemophilia, metabolic disorders, lysosomal storage disorders, and others. For a successful delivery of the transgene and sustained expression, the protocol must avoid immune responses in order to be efficacious. A growing number of studies have demonstrated that liver-directed transfer can induce transgene product-specific immune tolerance. Tolerance obtained via this route requires optimal engineering of the vector to eliminate transgene expression in antigen presenting cells while restricting high levels of therapeutic expression to hepatocytes. Innate immune responses may prevent tolerance induction, cause toxicity, and have to be minimized. Discussed in our review is the crucial role of CD4+CD25+ regulatory T cells in tolerance to the hepatocyte-derived gene product, the immunobiology of the liver and our current understanding of its tolerogenic properties, current and proposed research as to the mechanisms behind the livers unique cellular environment, as well as development of the tools for tolerance induction such as advanced vector systems.
Export Options
About this article
Cite this article as:
LoDuca A. Paul, Hoffman E. Brad and Herzog W. Roland, Hepatic Gene Transfer as a Means of Tolerance Induction to Transgene Products, Current Gene Therapy 2009; 9 (2) . https://dx.doi.org/10.2174/156652309787909490
DOI https://dx.doi.org/10.2174/156652309787909490 |
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
-
Leptin and Interleukin-1β Modulate Neuronal Glutamate Release and Protect Against Glucose-Oxygen-Serum Deprivation
Current Neurovascular Research Innate Immunity and Intracellular Trafficking: Insights for Novel Anti- HIV-1 Therapeutics
Current Pharmacogenomics Clinical and Therapeutic Challenges when Psychiatric Disorders Occur in Neurological Diseases: A Narrative Review
Current Psychiatry Research and Reviews Small Molecule Antagonists of the Chemokine Receptor CCR5
Current Topics in Medicinal Chemistry Antimicrobial and Structural Properties of Metal Ions Complexes with Thiosemicarbazide Motif and Related Heterocyclic Compounds
Current Medicinal Chemistry Emerging Use of Nanotechnology in the Treatment of Neurological Disorders
Current Pharmaceutical Design Response of Feline Immunodeficiency Virus (FIV) to Tipranavir May Provide New Clues for Development of Broad-Based Inhibitors of Retroviral Proteases Acting on Drug-Resistant HIV-1
Current HIV Research Impairment of T Cell Immunity by the Respiratory Syncytial Virus: Targeting Virulence Mechanisms for Therapy and Prophylaxis
Current Medicinal Chemistry Vaccines for Patients with COPD
Recent Patents on Inflammation & Allergy Drug Discovery A Clinical Perspective: Anti Taus Treatment in Alzheimers Disease
Current Alzheimer Research Possible Exploitation of Non-Neuronal and Non-Chemical Synaptic Signalling Pathways in Epilepsy Therapy
Current Signal Transduction Therapy Molecular Mechanisms Determining Opposed Functional States of Microglia
Current Neuropharmacology Regulatory T Cells and Tolerogenic Dendritic Cells as Critical Immune Modulators in Atherogenesis
Current Pharmaceutical Design Immune Checkpoint Inhibitors and Neurotoxicity
Current Neuropharmacology Therapeutic Approach to Multiple Sclerosis by Novel Oral Drugs
Recent Patents on Inflammation & Allergy Drug Discovery Toll-Like Receptors and Inflammation in the CNS
Current Drug Targets - Inflammation & Allergy Functions of Antimicrobial Peptides in Vertebrates
Current Protein & Peptide Science Recent Advances in Targeting Viral Proteases for the Discovery of Novel Antivirals
Current Topics in Medicinal Chemistry Immune Senescence and Vaccination in the Elderly
Current Topics in Medicinal Chemistry Anti-Inflammatory Drugs in Psychiatry
Inflammation & Allergy - Drug Targets (Discontinued)