Lentiviral vectors for gene therapy of cystic fibrosis
| Autor: | Po-Shun Lee, Mitchell J. Goldman, Joo-Sung Yang, James M. Wilson |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Cystic Fibrosis
Genetic enhancement Genetic Vectors Cystic Fibrosis Transmembrane Conductance Regulator Gene Expression Cystic fibrosis Virus Viral vector Transduction (genetics) Genes Reporter Genetics medicine Animals Humans Molecular Biology Tropism biology Lentivirus Gene Transfer Techniques HIV Epithelial Cells Genetic Therapy biology.organism_classification medicine.disease Cell Transformation Viral Virology Cystic fibrosis transmembrane conductance regulator Lac Operon biology.protein Molecular Medicine Moloney murine leukemia virus |
| Zdroj: | Human gene therapy. 8(18) |
| ISSN: | 1043-0342 |
| Popis: | A replication-defective vector based on human immunodeficiency virus (HIV) was evaluated for gene transfer directed to the lung. The tropism of this vector has been expanded through the incorporation of the vesticular stomatitis virus G protein into its envelope. The HIV vector effectively transduced nondividing airway epithelial cells in vitro whereas a murine-based retroviral vector did not. Experiments in a human bronchial xenograft model demonstrated high-level gene transduction with a cystic fibrosis transmembrane conductance regulator (CFTR) HIV vector into undifferentiated, cystic fibrosis (CF)-derived cells of the xenograft. CFTR expression was stable and capable of functional correction of the CF defect after the graft matured. The HIV vector did not effectively transduce cells of the xenograft when instilled after the epithelium had differentiated. This block to transduction appears to be at the level of entry, although post entry restrictions cannot be ruled out. Further development of this vector system for CF gene therapy should focus on a better understanding of potential entry and post entry blocks. |
| Databáze: | OpenAIRE |
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