Abstract
Recent studies have shed light on a number of important obstacles to safe and effective gene transfer to the respiratory tract with recombinant AAV vectors. Among these are blocks at the level of receptor binding and internalizations, evasion of proteasomal degradation, inefficiency of nuclear entry, and nuclear factors that inhibit the conversion of rAAV genomes into active double-stranded DNA form. Other important issues have been the size constraints of the vector, the lack of retention of episomal forms of the vector genome, and immune responses which may limit the efficiency of repeated doses of rAAV. Each of these potential obstacles has been addressed with new vector designs. In addition, the availability of an abundance of novel rAAV serotypes, each with its own receptor tropism, has expanded the range of possibilities for long-term success of gene therapy in the respiratory tract.
Keywords: cystic fibrosis (cf), alpha antitrypsin(aat), raav-mediated gene therapy, capsid mutants, proteasomal degradation, xenografts, tyrosine kinase inihbitors, split-intron vector
Current Gene Therapy
Title: Recent Developments in Recombinant AAV-Mediated Gene Therapy for Lung Diseases
Volume: 5 Issue: 3
Author(s): Terence R. Flotte
Affiliation:
Keywords: cystic fibrosis (cf), alpha antitrypsin(aat), raav-mediated gene therapy, capsid mutants, proteasomal degradation, xenografts, tyrosine kinase inihbitors, split-intron vector
Abstract: Recent studies have shed light on a number of important obstacles to safe and effective gene transfer to the respiratory tract with recombinant AAV vectors. Among these are blocks at the level of receptor binding and internalizations, evasion of proteasomal degradation, inefficiency of nuclear entry, and nuclear factors that inhibit the conversion of rAAV genomes into active double-stranded DNA form. Other important issues have been the size constraints of the vector, the lack of retention of episomal forms of the vector genome, and immune responses which may limit the efficiency of repeated doses of rAAV. Each of these potential obstacles has been addressed with new vector designs. In addition, the availability of an abundance of novel rAAV serotypes, each with its own receptor tropism, has expanded the range of possibilities for long-term success of gene therapy in the respiratory tract.
Export Options
About this article
Cite this article as:
Flotte R. Terence, Recent Developments in Recombinant AAV-Mediated Gene Therapy for Lung Diseases, Current Gene Therapy 2005; 5 (3) . https://dx.doi.org/10.2174/1566523054064986
DOI https://dx.doi.org/10.2174/1566523054064986 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
- 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
-
Selective Sensitization to Penicillin V with Tolerance to Other Betalactams
Recent Patents on Inflammation & Allergy Drug Discovery ACE Inhibitor Delapril Prevents Ca<sup>2+</sup>-Dependent Blunting of I<sub>K1</sub> and Ventricular Arrhythmia in Ischemic Heart Disease
Current Molecular Medicine Crofelemer: In HIV Associated Diarrhea and Secretory Diarrhea - A Patent Perspective
Recent Patents on Anti-Infective Drug Discovery Recent Advances in Management of Diabetic Macular Edema
Current Diabetes Reviews An Update on the Systemic Therapy of Malignant Salivary Gland Cancers: Role of Chemotherapy and Molecular Targeted Agents
Current Medicinal Chemistry - Anti-Cancer Agents Opioids: Other Routes for Use in Recovery Room
Current Drug Targets Systematic Review and Meta-analysis of Flibanserin's Effects and Adverse Events in Women with Hypoactive Sexual Desire Disorder
Current Drug Metabolism Anti-Inflammatory Treatments for Chronic Diseases: A Review
Inflammation & Allergy - Drug Targets (Discontinued) Prevention and Medical Treatment of Pouchitis In Ulcerative Colitis
Current Drug Targets Magnetic Resonance Imaging of Short T2 Relaxation Components in Tissue Using Ultrashort Echo Time (UTE) Pulse Sequences
Current Medical Imaging Two Different Functions of Doxycycline Which is Both An Antimicrobial Agent and An Immune Modulator
Anti-Infective Agents in Medicinal Chemistry Factors that Control the Circulation Time of Nanoparticles in Blood: Challenges, Solutions and Future Prospects
Current Pharmaceutical Design Pneumococcal Infections at Hajj: Current Knowledge Gaps
Infectious Disorders - Drug Targets Anti-Inflammatory and Anti-Allergy Drugs in Rhinosinusitis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Microaspiration in Intubated Critically Ill Patients: Diagnosis and Prevention
Infectious Disorders - Drug Targets Preventing Ventilator-Associated Pneumonia - The Role of the Endotracheal Tube
Current Respiratory Medicine Reviews Respiratory Tract Manifestations of Rheumatic Diseases in Children
Current Respiratory Medicine Reviews Antileukotriene Treatment in Children with Asthma - New Patents
Recent Patents on Inflammation & Allergy Drug Discovery Malignancy in Common Variable Immune Deficiency: Report of Two Rare Cases of Gastrointestinal Malignancy and a Review of the Literature
Cardiovascular & Hematological Disorders-Drug Targets Intranasal Drug Delivery to the Central Nervous System: Present Status and Future Outlook
Current Pharmaceutical Design