Tuning Covalent Organic Frameworks for Nucleic Acid Loading: Toward Creating a Hierarchical Artificial Cell

Bottom-up artificial cells have been widely studied in fundamental life sciences and other valuable applications. However, common one-pot encapsulation construction strategies usually result in oversimplified structure. Herein, we successfully constructed a nucleus structure based on covalent organic frameworks (COFs) using two different spatiotemporal strategies for linear or circular DNAs, which was further combined with cell-free transcription and translation (CFTT) to construct an artificial cell. Linear DNAs could be adsorbed through the pore structures of the COFs. Circular plasmids could be encapsulated inside the COF structure through a template sacrifice method (COFcap-1). The pore sizes and microenvironment were crucial to the CFTT efficiency. Three artificial nucleus logic gates were constructed and realized information transmission between different artificial organelles. Finally, the DNAs adsorbed on the COFs were successfully encapsulated inside liposomes to construct artificial cells with the nucleus structure. This study not only investigates new applications of COFs but also opens up a new avenue toward constructing artificial cells with high hierarchy in structure using porous materials.