Abstract:
The precise regulation of fundamental cellular behaviors, such as cell adhesion, proliferation, migration, differentiation, and cell-cell interactions, is essential in multicellular organisms. The regulation of cellular behaviors largely relies on the receptor-mediated sensing and transduction of the extracellular ligands. The precise manipulation of ligand-induced receptor activation via molecular engineering approaches will offer fundamental insight into physiological processes, facilitating the rational design of cell-based therapeutics to treat diseases. DNA is a highly attractive biomolecule as it works through either genetically encoding the functional protein or rationally fabricating functional nanomaterials. Recently accumulated research in functional nucleic acids and DNA nanotechnology makes it possible to construct dynamic and complex nanodevices to modulate receptor-mediated signaling and cellular behaviors. This review summarizes the recent advances in state-of-art of DNA technologies in engineering the interaction between ligand and cell-surface receptor, mainly highlighting the design principles and the emerging applications of DNA-based nongenetic engineering strategies for receptor-mediated cellular behaviors. We expect that significant advancements in DNA-based engineering strategies will enable the emergence of applications in cell-based therapy in regenerative medicine and cancer immunotherapy.
摘要:
对基本细胞行为的精确调节,如细胞粘附,扩散,迁移,分化,和细胞间的相互作用,在多细胞生物中是必不可少的。细胞行为的调节很大程度上依赖于受体介导的细胞外配体的传感和转导。通过分子工程方法对配体诱导的受体激活的精确操作将提供对生理过程的基本见解,促进合理设计基于细胞的疗法来治疗疾病。DNA是一种极具吸引力的生物分子,因为它通过基因编码功能性蛋白质或合理制造功能性纳米材料来发挥作用。最近在功能核酸和纳米DNA技术方面积累的研究使得构建动态和复杂的纳米器件来调节受体介导的信号传导和细胞行为成为可能。这篇综述总结了DNA技术在工程化配体和细胞表面受体之间的相互作用方面的最新进展,主要强调基于DNA的非基因工程策略在受体介导的细胞行为中的设计原理和新兴应用。我们预计,基于DNA的工程策略的重大进展将使再生医学和癌症免疫疗法中基于细胞的治疗的应用得以出现。