Covalent Organic Frameworks as Nano‐Reservoir for Room Temperature RNA Storage

Abstract The emerging role of Ribonucleic acids (RNAs) as therapeutics is alluring. However, RNAs are extremely labile under ambient conditions and typically need to be stored in cryogenic conditions (−20 °C to −80 °C). Hence, storage, stabilization, and transportation of RNA under ambient conditions have been an arduous task and remain an unsolved problem. In this work, a guanidinium‐based ionic covalent organic framework (COF), TTG Cl with nanotubular morphology, was synthesized and used as nano‐reservoirs for room‐temperature storage of RNA. To understand the role of the nanotubular morphology and chemical nature of TTG Cl in stabilizing the RNA structure and for comparison purposes, a neutral COF, TMT‐TT, is synthesized and studied. Further, density functional theory (DFT) studies confirmed non‐covalent interaction between the COFs and the RNA nucleobases, facilitating reversible storage of RNA. RNA loaded in COFs was found to be resistant to enzymatic degradation when treated with RNase. Gel electrophoresis and sequencing confirmed the structural integrity of the recovered RNAs and their further processibility.