likelihood of patients being infected with the wild type virus is limited by selection 
of only seropositive patients, and by treatment of patients who are isolated from 
exposure to wild type viruses. Finally, co-infection with the wild type virus would 
place the defective virus at a distinct advantage for replication, resulting eventually 
in a wild type viral infection that would be self-limiting. 
(3) Containment of the recombinant virus: This is extremely important, and 
the risk that the virus could be transmitted to another person seems extraordinarily 
unlikely. Replication of the recombinant adenovirus is unlikely, and the risk of 
spread to other people has been minimized by isolation procedures, including hand 
washing and use of gowns, gloves, and masks. The small dose of virus further limits 
the potential risk of exposure to others. The patient will also not be removed from 
isolation until there are two consecutive nasal specimens that are negative for live 
virus. Finally, any environmental release would be most likely associated with a 
recombinant virus with no CFTR biological activity (see #2 above). 
(4) Risks associated with the procedures: 
a) The procedure of recombinant virus and vehicle administration to the 
nasal epithelium should have no substantial risk, i.e., there may be 
some discomfort from the position required to instill the virus or some 
local nasal pain, which will be limited by topical anesthesia. Drug 
sensitivity (lidocaine) is a risk, but is rare, and patients will be well 
screened by history for allergy. 
b) Measurement of nasal PD is well tolerated and does not produce 
significant discomfort. There is a theoretical possibility of infection at 
the site of the subcutaneous needle insertion; this has not been 
observed in more than 10 years of using this technique at UNC. 
c) Nasal washes and pharyngeal swabs are modestly uncomfortable, but 
are associated with no significant long-term risk. These are regularly 
employed in research studies at UNC. 
d) Blood sampling produces the possibility of modest discomfort and 
bruising without substantial long-term risk. 
e) Biopsy of the nasal epithelium will be associated with pain and 
discomfort, although these will be addressed with local anesthesia. 
The subjects face a small risk of bleeding after the biopsy is 
completed, but this potential complication will be addressed by 
standard ENT practices. 
f) Pulmonary function testing includes arterial blood gases; this 
procedure is associated with the risk of bleeding and bruise formation, 
and is somewhat uncomfortable. 
g) These patients will be subjected to relative isolation in a hospital 
room for -two weeks, and are likely to suffer some emotional distress 
related to this isolation. We will attempt to minimize this by 
providing television (including cable), and a VCR for movies and 
video games. We will also provide facilities for exercising (bicycle or 
Recombinant DNA Research, Volume 17 
