IN-VIVO GENE-THERAPY OF HEMOPHILIA-B - SUSTAINED PARTIAL CORRECTION IN FACTOR-IX-DEFICIENT DOGS
IN-VIVO GENE-THERAPY OF HEMOPHILIA-B - SUSTAINED PARTIAL CORRECTION IN FACTOR-IX-DEFICIENT DOGS
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DOI：
10.1126/science.8211118
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发表时间：
1993-10-01
期刊：
影响因子：
56.9
通讯作者：
WOO, SLC
中科院分区：
文献类型：
--
作者：
KAY, MA;ROTHENBERG, S;WOO, SLC
肝脏是基因治疗的模型器官。已经开发了一种通过将重组逆转录病毒载体直接输注到门静脉血管系统中进行体内肝基因转移的方法，这导致外源基因的持续表达。为了确定这些技术是否适用于血友病B患者的治疗，在血友病B犬模型中进行了临床前有效性研究。当犬因子IX互补DNA直接转导到体内受影响犬的肝细胞中时，动物组成型表达低水平的犬因子IX超过5个月。凝血因子的持续表达导致给药动物的全血凝血和部分凝血活酶时间减少。因此，血友病B患者的长期治疗可能是可行的直接肝基因治疗体内。
The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.