Reversible Re-programing of Cell-Cell Interactions

Reversible Re-programing of Cell-Cell Interactions
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DOI:
10.1002/anie.201310645
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发表时间:
2014-05-12
影响因子:
16.6
通讯作者:
Wagner, Carston R.
Wagner, Carston R.
中科院分区:
化学1区
文献类型:
--
作者:
Gabrielse, Kari;Gangar, Amit;Wagner, Carston R.

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设计和重新编程细胞表面的能力将为设计基于细胞和组织的治疗方法提供一种可行的合成生物学方法。描述了一种新的细胞表面工程策略,该策略使用脂质化学自组装纳米环(脂质csan),可用于用分子报告体或靶向配体对任何细胞表面进行稳定和可逆的修饰。在fda批准的一种无毒药物的作用下,纳米结构被迅速分解,细胞间的相互作用被逆转。与表达嵌合抗原受体(CARS)的基因工程t细胞类似,当活化的外周血单核细胞(PBMCs)被抗epcam -脂质csans功能化时,它们被证明可以选择性地杀死抗原阳性的癌细胞。综上所述,这些结果表明脂质- csan有潜力成为一种快速、稳定和通用的细胞表面可逆工程和细胞-细胞相互作用的方法。
The ability to engineer and re-program the surfaces of cells would provide an enabling synthetic biological method for the design of cell- and tissue-based therapies. A new cell surface-engineering strategy is described that uses lipid-chemically self-assembled nanorings (lipid-CSANs) that can be used for the stable and reversible modification of any cell surface with a molecular reporter or targeting ligand. In the presence of a non-toxic FDA-approved drug, the nanorings were quickly disassembled and the cell-cell interactions reversed. Similar to T-cells genetically engineered to express chimeric antigen receptors (CARS), when activated peripheral blood mononuclear cells (PBMCs) were functionalized with the anti-EpCAM-lipid-CSANs, they were shown to selectively kill antigen-positive cancer cells. Taken together, these results demonstrate that lipid-CSANs have the potential to be a rapid, stable, and general method for the reversible engineering of cell surfaces and cell-cell interactions.