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    • 3. 发明申请
    • MODIFIED AND FUSION ENHANCED ERYTHROCYTES, CELLS AND USES THEREOF
    • 改良和融合增强的ERYTHROCYTES,细胞及其用途
    • WO2010077290A1
    • 2010-07-08
    • PCT/US2009/006459
    • 2009-12-09
    • GLASER, Lawrence, F.
    • GLASER, Lawrence, F.
    • C12N5/00
    • C12N5/0641C12N5/0006C12N2510/00
    • The present invention provides modified fusion enhanced erythrocytes (or other cell types and synthetic cells) which comprise human viral receptor proteins, human viral coreceptor proteins and viral derived proteins capable of mediating entry of respective viruses into the modified erythrocytes, cells or pseudo-cells. The present invention also provides methods of using the fusion enhanced modified erythrocytes, cells or pseudo-cells for the treatment or prevention of viral infections. In one embodiment, the fusion enhanced modified erythrocytes of the present invention comprise CD4 and at least one HIV coreceptor, such as CXCR4 or CCR5 and as well, at least one of cholesterol rafts, fusin, actin, a viral derived protein such as fusion peptide derived from HIV GP 120 or HIV GP41 or a shorter protein derived from a long viral protein, such as a portion of HIV derived GP 120, or HIV GP41 such as the 23 N-terminal peptide of the HIV-I gp 41 protein (AVGIGALFLGFLGAAGSTMGARS) called FP23 (Fusion Peptide). These viral- fusion enhanced cells may also be electrostatic charge enhanced through further additions named in this invention. The minor addition of iron to these modified erythrocytes, in tolerable amouts, yields a greater static charge, per cell, and thus the initial attraction for HIV will be enhanced proffering better initial static bonding to the virion, followed by the strong covalent or hydrophobic bonding which signifies the commencement of the fusion event. The modified erythrocytes, when administered to an HIV patient, bind to the plasma virus and induce the injection of the HIV ribonucleoprotein complex into the cells. The entrapped viral content is sequestered within said cell for at least the period of time that the cell maintains its outer membrane integrity. The virus is thereafter either degraded or deactivated within the erythrocytes, cells or pseudo-cells, or destroyed by erythrophagocytosis.
    • 本发明提供了修饰的融合增强红细胞(或其他细胞类型和合成细胞),其包含能够介导各种病毒进入修饰的红细胞,细胞或假细胞的人类病毒受体蛋白,人类病毒共受体蛋白和病毒衍生蛋白。 本发明还提供了使用融合增强修饰的红细胞,细胞或假细胞来治疗或预防病毒感染的方法。 在一个实施方案中,本发明的融合增强的修饰的红细胞包含CD4和至少一种HIV共受体,例如CXCR4或CCR5,以及胆固醇筏,融合蛋白,肌动蛋白,病毒衍生蛋白如融合肽中的至少一种 衍生自HIV GP120或HIV GP41或来自长病毒蛋白的较短蛋白质,例如HIV衍生的GP120的一部分或HIV GP41,例如HIV-1 gp 41蛋白的23 N-末端肽(AVGIGALFLGFLGAAGSTMGARS )称为FP23(融合肽)。 这些病毒融合增强细胞也可以通过本发明中命名的进一步添加来增强静电电荷。 在可耐受的淀粉中,这些修饰的红细胞轻微添加铁会增加每个细胞的静电荷,从而增强对HIV的初始吸引力,从而提高对病毒粒子的更好的初始静态结合,然后进行强共价或疏水键合 这意味着融合事件的开始。 修饰的红细胞在施用于HIV患者时与血浆病毒结合并诱导将HIV核糖核蛋白复合物注入细胞。 包埋的病毒含量被隔离在所述细胞内至少在细胞保持其外膜完整性的时间段内。 此后,病毒在红细胞,细胞或假细胞内被降解或失活,或被红细胞增多症所破坏。