GENE THERAPY USING INTRA-HEPATIC METHODGENE THERAPY INTRA-HEPATIC METHOD

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 血友病是一种人类遗传性疾病，其特征是缺乏凝血因子IX，而凝血因子IX是完成凝块形成过程以防止创伤和手术期间失血所必需的。由于这种情况是由一个无效的性连锁抑制基因引起的，因此有很大的可能性通过基因治疗来纠正这种缺陷。因此，本研究的目的是确定逆行静脉递送含有编码因子IX的人基因的质粒至肝脏的技术可行性。肝脏是所有凝血因子的主要来源，因此是该手术的靶器官。此外，除了编码因子IX的质粒外，还将同时施用编码称为整合酶的酶的第二质粒。整合酶将有助于将因子IX基因插入宿主细胞DNA中。将通过血液测试确定因子IX基因的成功整合和狒狒肝脏的人因子IX的生产。如果这种策略看起来安全和有效，那么它可以用于治疗人类的因子IX缺乏型血友病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Hemophilia is a inherited condition in humans characterized by the absence of factor IX which is required to complete the process of clot formation to prevent blood loss during trauma and surgery. Since this condition is caused by a deffective sex-linked ressesive gene, there is a strong possibility of correcting the deffect by gene therapy. Therefore, the objective of this study is to determine the technical feasibility of retrograde venous delivery of plasmids containing human gene that codes for factor IX to the liver. Liver is the major source of all clotting factors and therefore is the target organ for this procedure. In addition, to the plasmid encoding for factor IX , a second plasmid encoding for an enzyme called integrase will be administered at the same time. Integrase will aid in inserting the factor IX gene in to the host cell DNA. Successful integration of the factor IX gene and production of human factor IX by the baboon liver will be determined by blood tests. If this strategy appears safe and functional, then it can be used for the treatment of factor IX deficient hemophilia in humans.