Adenosine-Triggered Dynamic and Transient Aptamer-Based Networks Integrated in Liposome Protocell Assemblies
Yu Ouyang, Yang Sung Sohn, Xinghua Chen, Rachel Nechushtai, Eli Pikarsky, Fan Xia, Fujian Huang, Itamar Willner
Abstract
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.