The basic concept of gene therapy involves introducing a gene into target cells to cure, prevent or slow down the progression of a disease.
CF is a good candidate for this technology as it is primarily caused by mutations in a single gene. A normal copy of the gene could be delivered to patients via topical delivery to the lung, not requiring invasive techniques or surgery. A gene complementation approach would also directly target the cause of the disease and could correct many aspects of the complex lung pathology.
A single therapy to treat the underlying defect could greatly reduce the high therapeutic burden that CF patients currently have to endure.
In addition, one therapy might be suitable to treat subjects with a wide variety of mutations in the CFTR gene, meaning that a single treatment strategy would be relevant to all patients.
Soon after the cloning of the CFTR gene, proof-of-principle was established when the Cl- conductance defect was corrected after delivery of a functional copy of human wild-type CFTR DNA to cells isolated from CF patients (Drumm, et al., 1990, Rich, et al., 1990), and in transgenic CF mice (Alton, et al., 1993, Hyde, et al., 1993).
Studies in humans followed quickly. CF for gene therapy has been tested in humans using both viruses and liposomes. Five of the liposome trials were undertaken by members of the UK CF Gene Therapy Consortium (Caplen et al., 1995, Gill et al., 1997, Porteous et al., 1997, Alton et al., 1999, Hyde et al., 2000). These early studies were concerned mainly with safety issues.
The amount of gene transfer achieved is similar for both systems and is probably still too small to have any real therapeutic benefit (however, it is important to note that none of these trials actually measured therapeutic benefit). At present the effect seen (gene expression) only lasts for a few days.