Study design (if review, criteria of inclusion for studies)
double-blinded study
Participants
10 subjects (treatment), 2 subjects (placebo).
Interventions
plasmid DNA expressing the CFTR cDNA complexed with DC-Chol/DOPE cationic liposomes or placebo. Each subject received three doses, administered 4 weeks apart.
Outcome measures
inflammation, toxicity or an immune response. Nasal epithelial cells were collected 4 days after each dose for a series of efficacy assays including quantitation of vector-specific DNA and mRNA, immunohistochemistry of CFTR protein, bacterial adherence, and detection of halide efflux ex vivo. Airway ion transport was also assessed in vivo by repeated nasal potential difference (PD) measurements.
Main results
There was no evidence of inflammation, toxicity or an immune response towards the DNA/liposomes or the expressed CFTR. On average, six of the treated subjects were positive for CFTR gene transfer after each dose. All subjects positive for CFTR function were also positive for plasmid DNA, plasmid-derived mRNA and CFTR protein.
Authors' conclusions
The efficacy measures suggest that unlike high doses of recombinant adenoviral vectors, DNA/liposomes can be successfully re-administered without apparent loss of efficacy.
Keywords: Adolescent; Adult; Gene Transfer Techniques; non pharmacological intervention - genetic& reprod; pharmacological_intervention;