Applications of Gene Therapy - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 290

Table 6.4 (Continued)

No. Vector System Comments Reference

5 Adenovirus Bronchoscopic delivery of Ad/ CFTR showed detectable

CFTR mRNA at high dose, with local inflammation in
most of the patients. However, aerosol delivery of Ad/ CFTR
showed detectable mRNA with no toxicity in patients

[180]

6 Adenovirus Bronchoscopic dose escalation study of Ad/ CFTR . Flu-

like symptoms and cell-mediated immune response were
observed at a high vector dose in CF patients

[181]

7 Adenovirus For the assessment of repetitive administration of Ad/ CFTR .

No difference was observed between treated and untreated
nostrils of the patients. With repetitive administration, there
was a reduction in the correction of chloride transport and
increased immune response to adenovirus

[182]

8 Adenovirus Repeated administration of Ad/ CFTR using endobronchial

spray in three doses. Vector-derived mRNA was observed
in patients in a dose-dependent pattern. However, repetitive
administration did not show any significant expression

[183]

9 Adeno-

associated
virus

Bronchoscopic administration of AVV/ CFTR in one
nostril of patients resulted in CFTR expression in the lung

[184]

10 Adeno-

associated
virus

An escalating dose of AVV/ CFTR using maxillary
sinus route resulted in CFTR expression

[185]

11 DC-Chol/

DOPE
liposomes

Direct application of DC-Chol/DOPE/ CFTR to the
nasal epithelium of CF patients. Five of the eight
patients exhibited plasmid DNA and CFTR mRNA,
with no significant adverse effect

[186]

12 DC-Chol/

DOPE

Six of eight patients given DC-Chol/DOPE/ CFTR to
nasal epithelium showed partial correction of chloride
secretion. However, in two patients chloride responses
were within the non-CF range. Changes in chloride
correction were sustained for up to 7 days

[187]

13 DOTAP Seven out of eight patients exhibited CFTR DNA.

However, mRNA was detected in two patients

[188]

14 DC-Chol/

DOPE

Repeated administration of DC-Chol/DOPE/ CFTR
system was found to express CFTR efficiently and safely,
and it was well tolerated

[189]

16 GL-67 Liposomes were delivered to the lungs and noses of

patients. Partial correction of chloride secretions was
evident from potential difference measurements, but no
detection of CFTR mRNA was observed. Adverse effects
were reported in patients

[190]

17 GL-67 A safety assessment of an escalating dose of GL-6-based

liposomes in normal subjects showed that respiratory
symptoms were not present when liposome alone was
delivered

[191]