Ouyang Yu, Sohn Yang Sung, Chen Xinghua, Nechushtai Rachel, Pikarsky Eli, Xia Fan, Huang Fujian, Willner Itamar
Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
J Am Chem Soc. 2025 Jun 4;147(22):19282-19295. doi: 10.1021/jacs.5c05090. Epub 2025 May 22.
The development of transient dissipative nucleic-acid-based reaction circuits and constitutional dynamic networks attracts growing interest as a means of emulating native dynamic reaction circuits. Recent efforts applying enzymes, DNAzymes, or light as catalysts controlling the transient, dissipative functions of DNA networks and circuits were reported. Moreover, the integration of the dynamic networks in protocell assemblies and the identification of potential applications are challenging objectives. Here, we introduce the adenosine (AD) aptamer subunit complex coupled with adenosine deaminase (ADA) as a versatile recognition/catalytic framework for driving transient allosterically AD-stabilized DNAzyme circuits or dissipative AD-stabilized constitutional dynamic networks. In addition, the AD/ADA-driven transient frameworks are integrated into liposome assemblies as protocell models. Functionalized liposomes carrying allosterically ATP-stabilized DNAzymes cleaving EGR-1 mRNA are fused with MCF-7 breast cancer cells, demonstrating effective gene therapy and selective apoptosis of cancer cells.
作为模拟天然动态反应回路的一种手段，基于核酸的瞬态耗散反应回路和组成动态网络的发展引起了越来越多的关注。最近有报道称，人们努力应用酶、脱氧核酶或光作为催化剂来控制DNA网络和回路的瞬态耗散功能。此外，将动态网络整合到原始细胞组装体中以及确定潜在应用是具有挑战性的目标。在这里，我们引入了与腺苷脱氨酶（ADA）偶联的腺苷（AD）适配体亚基复合物，作为一种通用的识别/催化框架，用于驱动瞬态变构AD稳定的脱氧核酶回路或耗散性AD稳定的组成动态网络。此外，AD/ADA驱动的瞬态框架被整合到脂质体组装体中作为原始细胞模型。携带变构ATP稳定的脱氧核酶切割EGR-1 mRNA的功能化脂质体与MCF-7乳腺癌细胞融合，证明了有效的基因治疗和癌细胞的选择性凋亡。
