Gene Therapy for Cardiovascular Disease Using Hepatocyte Growth Factor

2006 ◽  
Vol 902 (1) ◽  
pp. 369-376 ◽  
Author(s):  
RYUICHI MORISHITA ◽  
MOTOKUNI AOKI ◽  
SHIGEFUMI NAKAMURA ◽  
JITSUO HIGAKI ◽  
YASUFUMI KANEDA ◽  
...  
2000 ◽  
Vol 118 (4) ◽  
pp. A1014
Author(s):  
Masaharu Takeuchi ◽  
Hiranari Kanemura ◽  
Takahiro Ueki ◽  
Kiyoshi Horiguchi ◽  
Yasukane Asano ◽  
...  

Hypertension ◽  
2004 ◽  
Vol 44 (2) ◽  
pp. 203-209 ◽  
Author(s):  
Ryuichi Morishita ◽  
Motokuni Aoki ◽  
Naotaka Hashiya ◽  
Hirofumi Makino ◽  
Keita Yamasaki ◽  
...  

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3924-3932 ◽  
Author(s):  
Lingfei Xu ◽  
Cuihua Gao ◽  
Mark S. Sands ◽  
Shi-Rong Cai ◽  
Timothy C. Nichols ◽  
...  

AbstractHemophilia B is a bleeding disorder resulting from factor IX (FIX) deficiency that might be treated with gene therapy. Neonatal delivery would correct the disease sooner than would transfer into adults, and could reduce immunological responses. Neonatal mice were injected intravenously with a Moloney murine leukemia virus–based retroviral vector (RV) expressing canine FIX (cFIX). They achieved 150% to 280% of normal cFIX antigen levels in plasma (100% is 5 μg/mL), which was functional in vitro and in vivo. Three newborn hemophilia B dogs that were injected intravenously with RV achieved 12% to 36% of normal cFIX antigen levels, which improved coagulation tests. Only one mild bleed has occurred during 14 total months of evaluation. This is the first demonstration of prolonged expression after neonatal gene therapy for hemophilia B in mice or dogs. Most animals failed to make antibodies to cFIX, demonstrating that neonatal gene transfer may induce tolerance. Although hepatocytes from newborns replicate, those from adults do not. Adult mice therefore received hepatocyte growth factor to induce hepatocyte replication prior to intravenous injection of RV. This resulted in expression of 35% of normal cFIX antigen levels for 11 months, although all mice produced anti-cFIX antibodies. This is the first demonstration that high levels of FIX activity can be achieved with an RV in adults without a partial hepatectomy to induce hepatocyte replication. We conclude that RV-mediated hepatic gene therapy is effective for treating hemophilia B in mice and dogs, although the immune system may complicate gene transfer in adults.


Gene Therapy ◽  
2011 ◽  
Vol 19 (8) ◽  
pp. 836-843 ◽  
Author(s):  
Y-N Jin ◽  
M Inubushi ◽  
K Masamoto ◽  
K Odaka ◽  
I Aoki ◽  
...  

2006 ◽  
Vol 345 (4) ◽  
pp. 1517-1525 ◽  
Author(s):  
Takamasa Kanbe ◽  
Rie Murai ◽  
Tomoyuki Mukoyama ◽  
Yoshiyuki Murawaki ◽  
Ko-ichi Hashiguchi ◽  
...  

2002 ◽  
Vol 49 (3) ◽  
pp. 273-284 ◽  
Author(s):  
RYUICHI MORISHITA ◽  
MOTOKUNI AOKI ◽  
YOSHIKAGE YO ◽  
TOSHIO OGIHARA

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