To address the issue of mRNA leakage from ZIF-8, we introduced linear 20 kDa, polycationic polyethyleneimine (PEI) into the synthetic process. PEI has been utilized in several studies to improve the material loading of mRNA as well as a stand-alone commercial reagent for transfection with mixed results. PEI is also a well-known metal chelator, especially of Zn 2+ , and a ZnO and ZIF-8 particle capping agent. The linear 20 kDa PEI isoform was chosen because lower molecular weight and branched isoforms have proven less efficient at gene delivery for various documented reasons and are supported by our findings (Figure ). The minimum amount of PEI needed to bind all mRNA was determined through a retardation assay, where PEI and mRNA were combined at various weight ratios. The minimum binding ratio of mRNA and PEI occurred at a weight ratio of (RNA: PEI) 1:0.8, which represents a nitrogen-to-phosphate (N/P) ratio of about 6 (Figure , Calculation 1).