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Efficient liver gene transfer with foamy virus vectors

机译：用泡沫病毒载体高效地进行肝脏基因转移

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Background Liver gene transfer offers hope for the correction of genetic and acquired disorders. Efficient gene transfer in large animals can be obtained with hydrodynamic gene transfer (HGT), a method that can achieve sufficient levels of gene delivery. Material and Methods To test the relative efficiency between plasmid versus foamy virus (FV) vector-based liver gene transfer efficiency, we applied HGT in 4 juvenile pigs, using the same plasmid backbone, either naked or coated as a FV vector particle. Gene transfer efficiency and persistence of expression was assayed by PCR and real-time PCR, respectively, at 1 week and at 1 month after the infusions. Results HGT was tolerated well and no adverse reactions were observed. Plasmid injections resulted in no detectable DNA sequences at 1 week. At the 1 month time point, 2/15 liver sections analyzed were positive for the presence of plasmid DNA. When FV vectors were infused under identical conditions, 18/28 (64.3%) of the liver samples were positive for the presence of vector sequences, and the expression levels reached 29.7 and 15.6% of the endogenous GAPDH levels in the injected and the adjacent liver lobes. Conclusions Our results indicate that medium-term therapeutic levels of gene expression can be obtained with FV vectors, an effect that can be attributed to the potential of the HGT procedure and to the natural affinity of FV vectors for hepatocytes.
机译：背景肝基因转移为纠正遗传性和获得性疾病提供了希望。可以通过流体动力学基因转移（HGT）获得大型动物的有效基因转移，该方法可以实现足够水平的基因转移。材料和方法为了测试基于质粒与泡沫病毒（FV）载体的肝基因转移效率之间的相对效率，我们将HGT应用于4头小猪，使用相同的质粒主链，裸或包被作为FV载体颗粒。输注后1周和1个月分别通过PCR和实时PCR检测基因转移效率和表达持久性。结果HGT耐受性良好，未见不良反应。质粒注射在1周时未检测到DNA序列。在1个月的时间点，分析的2/15肝切片中质粒DNA的存在为阳性。当在相同条件下注入FV载体时，有18/28（64.3％）的肝样品中存在载体序列阳性，并且在注射的肝和邻近肝脏中表达水平分别达到内源GAPDH的29.7和15.6％裂片。结论我们的结果表明，使用FV载体可以达到基因表达的中期治疗水平，这一作用可以归因于HGT程序的潜力以及FV载体对肝细胞的天然亲和力。

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