The Role of Proteoglycans in Retroviral Mediated Gene Transfer

9800617 Yarmush该SGER提案涉及使用重组逆转录病毒增加通常转移到哺乳动物细胞的有效性。 在以前的研究中，PI发现病毒生产细胞产生的糖蛋白抑制逆转录病毒介导的基因转移。 降解这些蛋白聚糖的酶提高了基因转移到哺乳动物细胞的生产率。 由于蛋白多糖和病毒颗粒的大小相似，物理分离似乎不太可能。 该提案的总体目标是更好地了解蛋白聚糖在抑制过程中的作用。 这将通过以下方式实现： 蛋白多糖的分离纯化及初步研究 它们的影响，以及它们的蛋白质和聚糖 片段传递过程 测量这些抑制剂与两种细胞的结合， 靶细胞和逆转录病毒。 识别抑制剂 片段和细胞受体负责 抑制作用 建立抑制过程的模型 更好地了解抑制机制及其范围应有助于发现解决问题的途径。 已经考虑过的一种这样的途径包括掺入破坏蛋白聚糖的基因。 ***

9800617 Yarmush This SGER proposal deals with increasing the effectiveness often transfer to mammalian cells using recombinant retroviruses. In previous efforts, the PIs have found that glycoproteins produced by virus producer cells inhibit retroviral-mediated gene transfer. Enzymes that degrade these proteoglycans enhance the productivity of the gene transfer to mammalian cells. Since the size of the proteoglycans and the viral particles are similar, physicals separations seem unlikely. The overall goal of this proposal is to better understand the role of the proteoglycans in the inhibition process. This will be accomplished by: Isolating and purifying the proteoglycans and studying their impact, and the impact of their protein and glycan fragments on the transfer process Measuring the binding of these inhibitors to both the target cells and the retrovirus. Identify the inhibitor fragment and the cell receptor responsible for the inhibition. Develop a model of the inhibition process A better understanding of the inhibition mechanism and its scope should facilitate discovery of routes to remedy the problem. One such route already considered involves incorporation of genes for proteoglycan destruction. ***