Building on this need for deeper molecular insights, recent work by Reineke and coworkers introduced versatile quinine-based polymers capable of delivering multiple cargos, including plasmid DNA, mRNA, and CRISPR/Cas9 machinery. Their studies suggest that the ability of these delivery systems to robustly accommodate and deliver these different types of cargoes is facilitated by their ability to bind them through multiple mechanisms, including electrostatic, π-stacking, and hydrogen bonding interactions . This insight opens new avenues for investigating similar phenomena in PEI-based systems, whose interactions with nucleic acid cargo have historically been assumed to be merely electrostatic in nature. Interestingly, a few computational studies have predicted that branched PEI (BPEI) might engage in additional binding modes beyond electrostatics . However, there has not been any experimental evidence to confirm this.