Time course of gene expression after the injection of adenoviral vectors containing CTLA4IG gene.
BACKGROUND
In vivo gene transfection using a recombinant adenoviral vector leads to diminished gene expression in a time-dependent manner that disappears within 4 weeks. CTLA4Ig blocks CD28-mediated costimulatory signal, and inhibits immune responses. We investigated the duration of transgene expression after administration of adenoviral vector containing CTLA4Ig gene (AdCTLA4Ig).


METHODS
We injected 1 x 10(9) plaque forming units (pfu) of AdCTLA4Ig into rats (n = 7) via the tail vein. Thereafter, the blood samples were collected for assay of serum CTLA4Ig levels using enzyme-linked immunosorbent assay.


RESULTS
The CTLA4Ig level reached the maximum (range, 65-86 microg/mL; average, 75 microg/mL) on days 3 to 5 after injection. Detectable levels of CTLA4Ig were observed up to 49 days. When we injected AdCTLA4Ig in combination with FTY720 administration, the maximum levels were higher and the detectable levels persisted longer.


CONCLUSIONS
Because directly injected adenoviral transgene expression had been reported to disappear between 21 to 30 days, we conclude that AdCTLA4Ig inhibits the immune response and prolongs the transgene (CTLA4Ig gene) expression. Some additional immunosuppressants, like FTY720, may be useful to enhance AdCTLA4Ig effects.
Kita
Y
Y
Department of Thoracic Surgery, Haibara General Hospital, Japan. kita38@haibara-hp.jp
Nogimura
H
H
Ida
M
M
Ozawa
Y
Y
Kageyama
Y
Y
Ohi
S
S
Ito
Y
Y
Matsushita
K
K
Takahashi
T
T
Suzuki
K
K
Kazui
T
T
Hayashi
S
S
Enosawa
S
S
Li
X-K
XK
Suzuki
S
S
D000069594:Abatacept; D000256:Adenoviridae; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D018796:Immunoconjugates / Q000097:blood / Q000235:genetics*; D007700:Kinetics; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection
D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; D000069594:Abatacept