Among the non-viral gene delivery vectors, poly(β-aminoester)s (pBAEs), a promising class of cationic polymers, offer low cytotoxicity, high transfection capacity, and biodegradable profile, the attributes desirable for an ideal vector . pBAEs display outstanding encapsulation and transfection efficiency, which is provided by a balanced combination of hydrophobicity and functional groups with protonation capacity. Electrostatic interactions with oligonucleotides, in addition to a fine-tuned hydrophobicity, enables pBAEs to offer enhanced encapsulation ability . The protonation of tertiary amines by the lower pH of endosomal compartment builds up osmotic pressure that eventually leads to endosomal escape. Moreover, pBAEs can be functionalized at terminal acrylates with cationic oligopeptides such as arginine (R), lysine (K), and histidine (H) via a thia-Michael addition reaction to form oligopeptide end-modified pBAEs (OM-pBAEs). OM-pBAEs enable enhanced polynucleotide encapsulation, cellular internalization, and transfection, both in vitro and in vivo .