Table 4.

Strategies to improve gene transfer efficacy of nonviral vectors.

Barriers	Functional moieties	Approaches	Materials/molecules used
Extracellular stability	Carrier molecules, hydrophobic moiety	DNA condensation protects from nucleases steric stability achieved by surface charge shielding	Protamine, lipids, gelation, PEGylation
Internalization	Targeting ligands	Receptor-mediated endocytosis	Transferrin, EGF, antibodies, RGD
Intracellular trafficking	Endosomal disruptive agent	Escape from endosomes and unpacking by proton sponge effect	PEI, DOPE
Nuclear entry	Nuclear localization signal	Nuclear entry	Tat, ReV

DNA: Deoxyribonucleic acid; EGF: epidermal growth factor; RGD: arginyl-glycylaspartic acid; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, Tat: HIV-1-transactivating protein; ReV: HIV-1 Rev protein; PEI: polyethyleneimine.