Long-lasting correction of the basic defect in cystic fibrosis

Funded Activity Summary

The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special virus delivery-particles, after conditioning the airway to make it receptive to the particles. The method works in normal mice and in CF mice; it gives long lasting gene transfer from a single dose and seems to affect all airway cell types. The gene transfer may also be occurring in airway stem cells, i.e. the mother cells from which grow all the cells of the airway surface. Until now, no-one else has been able to produce prolonged gene transfer in this way, nor arrange gene transfer into stem cells in live airways. There are now a number of things that we must investigate before we could conduct safety and effectiveness trials in larger animals, or consider moving into clinical trials in humans. We need to understand exactly how our conditioning agent works and is it safe; measure how long the gene correction can last actually in our animals; decide if we can we re-dose animals (if needed) without losing effectiveness because of inflammation or immune responses that might occur; and decide how important the airway stem cells are in producing the length of the gene transfer. Because it has been difficult to measure gene correction in CF airways, we will also test new ways we have developed to measure how well the gene correction works in CF airways. The findings of this project will allow us to develop our method to where we can test it in larger animals, to provide a strong, long-lasting gene correction that will be safe for testing in human clinical trials.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $458,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Respiratory Diseases

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

airway diseases | airway epithelium | cystic fibrosis | gene therapy | inherited disease | paediatric respiratory disease | respiratory disease | respiratory disease in children | stem cells

Related Links