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.
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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 |
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