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KMID : 0387720080190010001
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Korean Journal of Blood Transfusion
2008 Volume.19 No. 1 p.1 ~ p.8
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Gene Therapy in Rats with a Lentiviral Vector Containing the Human Coagulation Factor IX Gene
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Kim Seung-Taik
Oh Tae-Geun
Jeon Hwang-Gyun
Kim Ok-Hee
Lee Sang-Mee
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Abstract
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Background: Hemophilia B is an inheritable X-linked bleeding disorder that occurs as a consequence of genetic alterations within the factor IX (IX) gene. In the present study, pseudotyped HIV-I-derived lentiviral vectors expressing human IX (lentivirus-IX) were assessed for the ability to produce an active human IX in the animals transduced with lentivirus-IX.
Methods: The IX concentrations and activated partial thromboplastin times (aPTT) were measured from the supernatants of HeLa cells that were transduced with lentivirus-IX. In an animal study, we injected 1?g of lentivirus-IX into the hind limbs of Sparague-Dawley (SD) rats. The IX concentrations were measured from the plasma of the vehicle injected rats and the plasma of the lentivirus-IX injected rats for 8 weeks.
Results: The in vitro expression of human IX was detected in a dose-dependent manner following the transduction of lentivirus-IX into the HeLa cells (control: 10±3 vs. 100 ng of lentivirus-IX: 1486±50 ng/mL, P＜0.05). The aPTT also showed the tendency of dose-dependent decrease (control: 83.9±0.5 vs. 50 ng of lentivirus-IX: 80.1± 0.8 sec), but this was not statistically significant. In the animal experiment, the plasma IX concentration from the lentivirus-IX transduced rats (n=3) was significantly increased compared to the vehicle-injected rats (n=4) (5.9±3.9 vs. 46.4±20.6 ng/mL) at post-injection 1 week.
Conclusion: This study demonstrated that in vivo delivery of lentiviral vectors expressing human IX to the muscle cells has the potential to be a therapeutic modality for hemophilia B.
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KEYWORD
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Lentivirus, Human factor IX, Gene therapy
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