Non-viral vectors in cystic fibrosis gene therapy: progress and challenges

2004 ◽  
Vol 22 (11) ◽  
pp. 586-592 ◽  
Author(s):  
T. Montier ◽  
P. Delépine ◽  
C. Pichon ◽  
C. Férec ◽  
D.J. Porteous ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Viral Vectors ◽  
Cystic Fibrosis Gene

scholarly journals Novel molecular approaches to cystic fibrosis gene therapy

2005 ◽  
Vol 387 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Tim W. R. LEE ◽  
David A. MATTHEWS ◽  
G. Eric BLAIR
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Bronchial Tree ◽  
Endosomal Escape ◽  
Host Cells ◽  
Cystic Fibrosis Gene ◽  
Viral Gene ◽  
Molecular Approaches

Gene therapy holds promise for the treatment of a range of inherited diseases, such as cystic fibrosis. However, efficient delivery and expression of the therapeutic transgene at levels sufficient to result in phenotypic correction of cystic fibrosis pulmonary disease has proved elusive. There are many reasons for this lack of progress, both macroscopically in terms of airway defence mechanisms and at the molecular level with regard to effective cDNA delivery. This review of approaches to cystic fibrosis gene therapy covers these areas in detail and highlights recent progress in the field. For gene therapy to be effective in patients with cystic fibrosis, the cDNA encoding the cystic fibrosis transmembrane conductance regulator protein must be delivered effectively to the nucleus of the epithelial cells lining the bronchial tree within the lungs. Expression of the transgene must be maintained at adequate levels for the lifetime of the patient, either by repeat dosage of the vector or by targeting airway stem cells. Clinical trials of gene therapy for cystic fibrosis have demonstrated proof of principle, but gene expression has been limited to 30 days at best. Results suggest that viral vectors such as adenovirus and adeno-associated virus are unsuited to repeat dosing, as the immune response reduces the effectiveness of each subsequent dose. Nonviral approaches, such as cationic liposomes, appear more suited to repeat dosing, but have been less effective. Current work regarding non-viral gene delivery is now focused on understanding the mechanisms involved in cell entry, endosomal escape and nuclear import of the transgene. There is now increasing evidence to suggest that additional ligands that facilitate endosomal escape or contain a nuclear localization signal may enhance liposome-mediated gene delivery. Much progress in this area has been informed by advances in our understanding of the mechanisms by which viruses deliver their genomes to the nuclei of host cells.

Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy

2014 ◽  
pp. 150127063140004
Author(s):  
Lee Adrian Davies ◽  
Graciela A Nunez-Alonso ◽  
Gerry McLachlan ◽  
Stephen C Hyde ◽  
Deborah Rebecca Gill
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Cystic Fibrosis Gene ◽  
Aerosol Delivery

Biology students' understanding of cystic fibrosis, gene therapy, and gene screening

1998 ◽  
Vol 32 (2) ◽  
pp. 103-110 ◽  
Author(s):  
Ruaraidh Hill ◽  
Helen O'Sullivan ◽  
Martin Stanisstreet ◽  
Edward Boyes
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Cystic Fibrosis Gene ◽  
Biology Students ◽  
Gene Screening
Sign in / Sign up

Export Citation Format

Share Document