Effects of a Brain-Engraftable Microglial Cell Line Expressing Anti-Prion scFv Antibodies on Survival Times of Mice Infected with Scrapie Prions
Effects of a Brain-Engraftable Microglial Cell Line Expressing Anti-Prion scFv Antibodies on Survival Times of Mice Infected with Scrapie Prions
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DOI：
10.1007/s10571-011-9696-z
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发表时间：
2011-10-01
影响因子：
4
通讯作者：
Sakaguchi, Suehiro
中科院分区：
文献类型：
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作者：
Fujita, Koji;Yamaguchi, Yoshitaka;Sakaguchi, Suehiro
我们首先证实了HEK293T细胞分泌了一个针对朊病毒蛋白的单链病毒片段（anti-PrP scFv），并阻止了朊病毒在感染细胞中的复制。然后，我们在小鼠脑移植小胶质细胞中稳定表达抗prp scFv，并在感染朊病毒之前或之后将这些细胞注入小鼠脑内。有趣的是，在感染前或感染后的早期时间点注射，轻微地减轻了感染，但显著延长了小鼠的生存时间。这表明，利用脑移植细胞进行抗prp scFvs的体外基因转移可能是一种针对朊病毒疾病的免疫治疗方法。
We first verified that a single chain Fv fragment against prion protein (anti-PrP scFv) was secreted by HEK293T cells and prevented prion replication in infected cells. We then stably expressed anti-PrP scFv in brain-engraftable murine microglial cells and intracerebrally injected these cells into mice before or after infection with prions. Interestingly, the injection before or at an early time point after infection attenuated the infection marginally but significantly prolonged survival times of the mice. These suggest that the ex vivo gene transfer of anti-PrP scFvs using brain-engraftable cells could be a possible immunotherapeutic approach against prion diseases.