New gene therapy research has been reported by scientists at University of Alabama
February 23rd, 2009
2009 FEB 23 -- According to recent research from the United States, "Cystic fibrosis (CF) is a common genetic disease characterized by defects in the expression of the CF transmembrane conductance regulator (CFTR) gene. Gene therapy offers better hope for the treatment of CF."
"Adeno-associated viral (AAV) vectors are capable of stable expression with low immunogenicity. Despite their potential in CF gene therapy, gene transfer efficiency by AAV is limited because of pathophysiological barriers in these patients. Although a few AAV serotypes have shown better transduction compared with the AAV2-based vectors, gene transfer efficiency in human airway epithelium has still not reached therapeutic levels. To engineer better AAV vectors for enhanced gene delivery in human airway epithelium, we developed and characterized mutant AAV vectors by genetic capsid modification, modeling the well-characterized AAV2 serotype. We genetically incorporated putative high-affinity peptide ligands to human airway epithelium on the GH loop region of AAV2 capsid protein. Six independent mutant AAV were constructed, containing peptide ligands previously reported to bind with high affinity for known and unknown receptors on human airway epithelial cells. The vectors were tested on nonairway cells and nonpolarized and polarized human airway epithelial cells for enhanced infectivity. One of the mutant vectors, with the peptide sequence THALWHT, not only showed the highest transduction in undifferentiated human airway epithelial cells but also indicated significant transduction in polarized cells. Interestingly, this modified vector was also able to infect cells independently of the heparan sulfate proteoglycan receptor," wrote A.F. White and colleagues, University of Alabama.
The researchers concluded: "Incorporation of this ligand on other AAV serotypes, which have shown improved gene transfer efficiency in the human airway epithelium, may enhance the application of AAV vectors in CF gene therapy."
White and colleagues published their study in Human Gene Therapy (Genetic Modification of Adeno-Associated Viral Vector Type 2 Capsid Enhances Gene Transfer Efficiency in Polarized Human Airway Epithelial Cells. Human Gene Therapy, 2008;19(12):1407-1414).
For additional information, contact S. Ponnazhagan, University of Alabama, Dept. of Pathology, LHRB 513 701, 19th St. S, Birmingham, AL 35294, USA.
Publisher contact information for the journal Human Gene Therapy is: Mary Ann Liebert Inc., 140 Huguenot Street, 3RD FL, New Rochelle, NY 10801, USA.
Keywords: United States, Birmingham, Biotechnology, Cystic Fibrosis, Fibrosis, Gene Therapy, Genetic Diseases, Genetic Modification, Genetics, Genomics, Hepatology, Medical Device, Physiology, Treatment, Viral, Virus, University of Alabama.
This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
