The safe and effective delivery of DNA and RNA therapeutics continues to be a major hurdle toward personalized medicine, mainly due to the digestion of this genetic material during endosomal uptake. Herein, we designed a hydrophobic nonionic urea-linked molecular clamp (mol-clamp) based on guanine and phenylalanine (GFUFG) that can readily complex nucleic acids and transport them into cells through passive diffusion. The optimal chiral self-assembled state was achieved by controlling the dimethyl sulfoxide to water ratio in the solvent mixture. Dictated by the presence of hydrophobic moieties in the mol-clamp, a secondary structure was formed through intermolecular hydrogen bonding. The negatively charged complex of mol-clamped nucleic acids was delivered in high efficiency as indicated by the signal of fluorescently labeled ssDNA to both the cytoplasm and the nucleus. The actual efficacy of GFUFG was further evaluated by delivering functional single-stranded DNA (DNAzyme) and siRNA (si-BCL-2), which downregulated EGR-1 and BCL-2 by 44% and 53%, respectively. We envisage that designing mol-clamps that can effectively complex genetic materials and promote passive diffusion rather than endocytosis can improve the field of biologics delivery for individualized therapy and cellular engineering.