Gene Therapy for CF using Cationic Liposome Mediated Gene Transfer: Phase I Trial 
Alabama at Birmingham, and he/she will continue to receive the best available standard 
treatment for CF. The patient agrees that by participation in this study, he/ she will not enter into 
another experimental study (for example, a rh DNase trial) at the same time. All standard CF 
therapy will remain available to the patient during his/her participation in this study. A decision 
not participate or to withdraw from the study will not effect a patient’s care at the University 
of Alabama at Birmingham, and he/she will continue to receive the best available standard 
treatment for CF. 
m.G. SUMMARY OF CLINICAL TRIAL 
The studies described here will provide information concerning the response in humans 
to application of lipid/DNA conjugates to a limited region of the nasal mucosa. The potential 
sequelae of administration, including inflammation or cytopathic effects at the site of gene 
delivery, as well as more distant effects such as humoral antibody responses to vector and DNA, 
as well as the duration of these responses, will be evaluated. Results from this study will provide 
useful information concerning cationic liposome-mediated delivery of ion transport competent 
CFTR, evaluation of CFTR protein and mRNA expression at the target site of gene transfer, 
information about optimal lipid: DNA ratios for use in human respiratory mucosal gene transfer 
using cationic liposomes, and the possible duration of CFTR expression after plasmid based 
DNA administration in human nasal mucosa. Because nasal respiratory epithelium is a well- 
established model for study of the CF ion transport abnormality which exists in the lower 
airways, results obtained in this protocol will be directly relevant to future therapies aimed at 
correcting the genetic defect which leads to CF. If safe, functional CFTR expression can be 
shown in nasal respiratory epithelium using cationic liposome-mediated gene transfer, this study 
will set the stage for administration of lipid/CFTR gene conjugates to the lower airways and 
possible amelioration of the progressive respiratory damage caused by mutant CFTR. Any 
information obtained in this study concerning the duration of functional CFTR effects on CFTR 
mRNA on protein expression or nasal bioelectric correction will also be significant, since this 
data will suggest an appropriate course for a future study of repeated CFTR gene administration 
within the nasal airway. On the other hand, substantial local or other toxicity will indicate the 
need to explore other cationic lipid formulations, both in vitro and in vivo , as well as alternate 
vector systems for gene delivery. By focusing this study on nasal rather than lower airway 
epithelium, the study will aim to evaluate important initial questions while placing the CF 
patients involved in the protocol at a minimum of risk. The results obtained from this study are 
highly likely to provide useful information concerning lipid mediated gene transfer as a potential 
therapy for cystic fibrosis. 
m.H. OVERALL ASSESSMENT OF RISKS AND BENEFITS IN THIS STUDY 
The risks involved in this study relate to nasal administration of lipid/DNA conjugates and the 
procedures designed to test safety and efficacy of gene delivery. 
a. Risks associated with DNA administration to nasal respiratory epithelium include local 
pain or irritation, and the discomfort associated with approximately one hour of lying 
very still in a lateral decubitus position. Attempts will be made to minimize these 
discomforts by use of topical anesthesia and mild oral sedation. The nasal mucosal target 
for gene delivery is at risk of local inflammation and/or cytopathic effects mediated by 
lipid/DNA conjugates. Although cationic liposomes are clearly toxic in vitro at high 
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Recombinant DNA Research, Volume 18 
