华东师范大学裴昊团队用DNA反应电路选择组装路径以编程调控多个细胞间的相互作用。 相关研究成果于2021年2月25日发表于国际顶尖学术期刊《美国化学会杂志》。

细胞间相互作用的调控促进了对多细胞行为的研究，但在具有多种细胞类型的复杂反应途径中对多细胞组装的编程调控仍然是一个巨大的挑战。

该文中，研究人员报告了一个基于DNA反应电路的可编程调节多种细胞-细胞相互作用细胞表面工程方法。DNA电路是基于茎环集成的DNA发夹基序设计的，该发夹基序具有通过顺序变构激活编程多种分子自组装和拆卸途径的能力。用这种DNA反应电路修饰细胞表面可以在细胞膜上执行可编程的化学功能，并且可以选择性地控制多细胞自组装。

研究人员证明了自然杀伤（NK）细胞对两种肿瘤细胞靶向能力的选择性控制，显示了选择性增强的细胞特异性适应性免疫治疗效果。研究人员希望该方法能为复杂反应途径中多种细胞间相互作用的可编程控制提供新的思路，并有可能促进细胞免疫治疗的发展。

附：英文原文

Title: Assembly Pathway Selection with DNA Reaction Circuits for Programming Multiple Cell–Cell Interactions

Author: Mingshu Xiao, Wei Lai, Huizhen Yu, Zijing Yu, Li Li, Chunhai Fan, Hao Pei

Issue&Volume: February 25, 2021

Abstract: The manipulation of cell–cell interactions promotes the study of multicellular behavior, but it remains a great challenge for programming multicellular assembly in complex reaction pathways with multiple cell types. Here we report a DNA reaction circuit-based approach to cell–surface engineering for the programmable regulation of multiple cell–cell interactions. The DNA circuits are designed on the basis of a stem-loop-integrated DNA hairpin motif, which has the capability of programming diverse molecular self-assembly and disassembly pathways by sequential allosteric activation. Modifying the cell surface with such DNA reaction circuits allows for performing programmable chemical functions on cell membranes and the control of multicellular self-assembly with selectivity. We demonstrate the selective control of targeting the capability of natural killer (NK) cells to two types of tumor cells, which show selectively enhanced cell-specific adaptive immunotherapy efficacy. We hope that our method provides new ideas for the programmable control of multiple cell–cell interactions in complex reaction pathways and potentially promotes the development of cell immunotherapy.

DOI: 10.1021/jacs.0c12358

Source: https://pubs.acs.org/doi/10.1021/jacs.0c12358