The amine groups of PEI allow for a wide range of post-polymerization modifications including carboxylation, acetylation, succinylation, hydroxylation, or PEGylation. These modifications help to optimize polymer/DNA interactions, decrease PEI charge density, lower cytotoxicity, enhance transfection efficacy, and mitigate particle aggregation. Focusing on acetylated and succinylated PEI, studies, including our own, have demonstrated increased nucleic acid delivery. Acetylation modifies PEI amines to uncharged acyl groups, while succinylation results in negatively charged succinyl groups, generating a polyampholytic or zwitterionic-like PEI (zPEI).