Seppen J, Barry S C, Harder B, Osborne W R
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA.
Blood. 2001 Aug 1;98(3):594-6. doi: 10.1182/blood.v98.3.594.
A lentivirus pseudotyped with vesicular stomatitis virus G protein (VSV-G) encoding rat erythropoietin (EPO) complementary DNA was administered to rat skeletal muscle and red blood cell production was serially monitored. After a single intramuscular injection hematocrit values increased and reached a plateau at about 35 days and were sustained for at least 14 months. Virus doses of 6 x 10(7) infectious units and 6 x 10(6) infectious units produced significantly increased mean hematocrit values of 68.5% +/- 2.1% (P <.001, n = 4) and 52.7% +/- 1.3% (P <.001, n = 3), respectively, over values of control animals receiving normal saline (46.2% +/- 1.5%, n = 2). A polymerase chain reaction (PCR) assay for vector sequences in genomic DNA showed muscle tissue at the site of injection was positive and undetectable in liver, spleen, kidney, and lung. The intramuscular administration of lentivirus provided a dose-responsive, highly efficient and sustained EPO gene delivery, suggesting these vectors may be applied generally to the systemic delivery of proteins such as hormones and clotting factors. (Blood. 2001;98:594-596)
将携带编码大鼠促红细胞生成素（EPO）互补DNA的水疱性口炎病毒G蛋白（VSV-G）假型化的慢病毒注射到大鼠骨骼肌中，并连续监测红细胞生成情况。单次肌肉注射后，血细胞比容值升高，在约35天时达到平台期，并持续至少14个月。6×10⁷感染单位和6×10⁶感染单位的病毒剂量分别使平均血细胞比容值显著升高至68.5%±2.1%（P<.001，n = 4）和52.7%±1.3%（P<.001，n = 3），高于接受生理盐水的对照动物（46.2%±1.5%，n = 2）。对基因组DNA中载体序列进行的聚合酶链反应（PCR）分析显示，注射部位的肌肉组织呈阳性，而在肝脏、脾脏、肾脏和肺中未检测到。慢病毒的肌肉内给药提供了剂量依赖性、高效且持续的EPO基因递送，表明这些载体可能普遍适用于激素和凝血因子等蛋白质的全身递送。（《血液》。2001年；98：594 - 596）
