Gene Therapy for CF using Canonic Liposome Mediaied Gene Transfer: Phase I Trial 
with minimal irritation but can be associated with sneezing or tearing. 
3. Nasal brushings and washings. These are moderately uncomfortable and will be 
performed after local anesthesia is provided. Pain, and the small risk of bleeding 
following the procedure, can be managed by applying gentle pressure directly to 
the site. Gentle swabs of the nasal mucosa are associated with minimal, if any, 
discomfort. 
4. Nasal endoscopy. Nasal endoscopy is a standard ENT procedure which involves 
modest discomfort, usually w-ell-managed with topical anesthesia and mild 
sedatives. The small risk of bleeding following the procedure exists; bleeding can 
be managed by direct pressure to the site with a cotton-tipped applicator or gauze. 
5. Nasal biopsy. Bilateral nasal biopsies are planned for each CF patient enrolled in 
this study (in order to exclude significant inflammation at the site of gene 
administration and to screen for wild-type CFTR expression at mRNA and protein 
levels). Biopsy of the nasal epithelium produces moderate pain and discomfort, 
and local anesthesia as well as oral anesthesia, if necessary, will be used to 
minimize these symptoms. There is also a small risk of bleeding and infection at 
the biopsy site, either of which can be generally addressed by appropriate 
treatment, e.g., applying pressure to the bleeding site under direct visualization; 
use of antibiotics to control infection. A small risk of associated scar formation 
at the biopsy site is also present. 
6. 12-lead EKG. sputum culture, and pulmonary function tests are routinely 
performed on CF patients and no significant risks from these tests are anticipated. 
7. Chest and sinus x-rays carry the risks associated with radiation exposure. 
Although no direct adverse affects attributable to the low doses of radiation used 
for the tests in this study have been demonstrated, the cumulative effects of 
radiation over a patient’s lifetime (particularly in the setting of multiple chest x- 
rays and other radiographic studies which CF patients undergo) is not known. 
8. Emotional discomfort attributable to a 5-day hospitalization may be significant. 
Television, reading materials, social service support, VCR, video games, etc., 
will be made available to patients during their hospitalization in the Clinical 
Research Center. 
c. Risks to hospital or other personnel. The risks for spread of lipid/DNA conjugates to 
hospital personnel and others is very low. There is no evidence that DNA prepared and 
transferred to eukayotic cells in the manner used in this study is capable of replication 
or independent gene transfer. However, because aerosolization of plasmid DNA 
complexed to lipid could occur during or immediately following the time of administra- 
tion into the patient’s nose (e.g., as a result of the patient sneezing) and since lipid DNA 
conjugates have been shown to mediate efficient gene transfer into murine lungs 
following aerosolization, respiratory precautions will be taken by all personnel during the 
first day of the patient’s admission to the CRC. 
Overall Risk-Benefit Ratio 
This is a Phase I study of administration of the CFTR gene to a very limited area of the 
respiratory epithelium. Because it is not anticipated that correction of the CF electrolyte 
transport abnormality within a small segment of the nasal airway will lead to any improvement 
[836] 
Recombinant DNA Resea r ch, Volume 18 
