Cell-penetrating peptides (CPPs), and metal-organic frameworks (MOFs) are promising as next-generation for the delivery of gene-based therapeutic agents. Oligonucleotide (ON)-mediated assembly of nanostructures composed of hierarchical porous zeolitic imidazolate framework (ZIF-8), and nanoparticles such as graphene oxide (GO), and magnetic nanoparticles (MNPs) for gene therapy are reported. Five different types of non-viral vectors (ZIF-8, RhB@ZIF-8, BSA@ZIF-8, MNPs@ZIF-8, and GO@ZIF-8), and three gene therapeutic agents (plasmid, splice correction oligonucleotides (SCO), and small interfering RNA (siRNA)) were investigated. The polyplexes were characterized and applied for gene transfection. The materials show very low toxicity with high efficiency for luciferase transfection. ZIF-8 enhances the transfection of plasmid, SCO, siRNA of CPPs by 2-8 folds. The mechanism of the cell uptakes was also highlighted. Data reveal cell internalization via scavenger class A (SCARA).