Gene Therapy for CF using Canonic Liposome Mediated Gene Transfer: Phase I Trial 
non-blinded, ascending dose administration of lipid/CFTR cDNA conjugates to nasal airway 
epithelium, similar in terms of target site to protocols previously approved by the Recombinant 
DNA Advisory Committee for the evaluation of recombinant adenovirus mediated CFTR 
delivery (Welsh and Smith, RAC Protocol #9212-036; Boucher and Knowles, RAC Protocol 
#9303-042). For each patient in the study, cationic liposomes will be used to deliver CFTR to 
one nostril, and a mock transfection (lipid/DNA conjugate lacking CFTR) of the contralateral 
nostril will be performed as a negative control. Three ascending dosages of CFTR cDNA will 
be utilized. The patients will not be paid for their participation in the study nor will a patient 
questionnaire or interview be utilized. 
m.B. Specific Aims of the Human Protocol 
1. Evaluate safety of lipid-mediated gene transfer to nasal epithelium of CF patients. Local 
inflammation and injury of the mucosal and sub-mucosal tissues will be evaluated following gene 
transfer, both in CFTR and (contralateral) mock transfected nasal epithelium. Systemic responses 
to the administered lipid/DNA conjugate (blood counts, serum chemistries, serologic antibody 
responses to the lipid or DNA) will also be addressed. 
2. Evaluate efficacy of wild-tvpe CFTR cDNA administration in CF nasal epithelium in 
vivo . Three ascending dosages of CFTR cDNA will be evaluated. Nasal respiratory epithelium 
will be studied for expression of CFTR protein and mRNA, for correction of the ion transport 
abnormality associated with the disease within nasal epithelium, and for the duration of these 
responses. 
TTT.C. Use of Nasal Epithelium for Recombinant Gene Administration 
Airway epithelium immediately below the inferior turbinate will serve as the target for 
gene transfer in these experiments. This epithelium is histologically similar to the epithelium of 
lower airways, and is readily accessible for studies of the effects of lipid-mediated gene transfer. 
CF airway epithelium within the nose 1) exhibits a well-characterized ion transport abnormality 
which parallels that observed in lower airway epithelium, 2) can be used to directly evaluate 
electrical correction of the CF defect following gene transfer and 3) allows studies of gene 
transfer without the complicating features of chronic, severe inflammation and scarring which 
characterize the lower airways. Additionally, by performing initial gene transfer in the nasal 
epithelium, the risks associated with repeated bronchoscopy (both for gene delivery and for 
evaluation following gene transfer) will not be included in this Phase I trial. 
TTf.D. Patient Evaluation 
Prior to and during the gene transfer protocol, a series of tests will be undertaken in 
order to establish baseline information relevant to the patient’s clinical status (severity of CF and 
non-CF related illnesses) and the magnitude of the transport abnormalities within the nasal 
epithelium of study participants. These tests include: 
1 . Complete history and physical examination, blood count and differential, blood chemistry 
evaluation including tests of liver function (transaminases, LDH, bilirubin), renal 
function (BUN, creatinine), serum electrolyte levels, and whole blood for CFTR 
genotype analysis. 
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Recombinant DNA Research, Volume 18 
