Cellular microvesicle pathways can be targeted to transfer genetic information between non-immune cells.
Cellular microvesicle pathways can be targeted to transfer genetic information between non-immune cells.
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DOI：
10.1371/journal.pone.0006219
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发表时间：
2009-07-13
期刊：
影响因子：
3.7
通讯作者：
Kurre P
中科院分区：
文献类型：
--
作者：
Skinner AM;O'Neill SL;Kurre P
真核细胞通讯是基于蛋白质信号级联，需要直接的细胞-细胞并置，或受体参与分泌的分子。遗传信息的传递被认为是不常见的，除了最近报道的免疫和胶质母细胞瘤细胞中的外泌体RNA转移。我们希望检查现有的微泡途径是否可以直接靶向RNA基因组在不太专业的细胞类型中的水平转移。使用复制缺陷型逆转录病毒载体，本文的研究证实，一系列细胞常规地将这些RNA基因组的小群体隔离在非规范区室中，其对抗体中和是难治的，并且不受常规病毒运输中涉及的途径的特异性药理学抑制的影响。我们的实验进一步揭示了载体基因组与四跨膜蛋白的细胞质共定位以及PI-3-激酶敏感的运输和随后传递到2°靶标。总的来说，我们的结果表明一个可扩展的过程，细胞路由载体基因组多泡体（MVB）的细胞质运输和外泌体释放。我们的研究结果表明，细胞可以用于递送重组有效载荷，靶向2°靶细胞的稳定遗传修饰。
Eukaryotic cell communication is based on protein signaling cascades that require direct cell-cell apposition, or receptor engagement by secreted molecules. The transmission of genetic information is thought to be uncommon, apart from recent reports of exosomal RNA transfer in immune and glioblastoma cells. We wished to examine if existing microvesicle pathways could be directly targeted for the horizontal transfer of RNA genomes in less specialized cell types. Using replication-deficient retrovirus vector, studies herein confirm that a range of cells routinely sequester a small population of these RNA genomes in a non-canonical compartment, refractory to antibody neutralization and unaffected by specific pharmacological inhibition of pathways involved in conventional viral trafficking. Our experiments further reveal the cytoplasmic colocalization of vector genomes with tetraspanin proteins as well as the PI-3-kinase sensitive trafficking and subsequent transmission to 2° targets. Collectively, our results indicate a scalable process whereby cells route vector genomes to multivesicular bodies (MVB) for cytoplasmic trafficking and exosomal release. Our findings imply that cells can serve to deliver recombinant payload, targeted for the stable genetic modification of 2° target cells.
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