Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung

摘要: High-molecular-mass polyethylenimines (PEIs) are widely used vectors for nucleic acid delivery. We found that removal of the residual N-acyl moieties from commercial linear 25-kDa PEI enhanced its plasmid DNA delivery efficiency 21 times in vitro, as well 10,000 mice with a concomitant 1,500-fold enhancement lung specificity. Several additional PEIs were synthesized by acid-catalyzed hydrolysis poly(2-ethyl-2-oxazoline), yielding pure polycations. PEI87 and PEI217 exhibited highest vitro: 115-fold 6-fold above those deacylated PEI25s, respectively; moreover, delivered to mouse efficiently PEI25 but at lower concentration 200-fold These improvements stem an increase number protonatable nitrogens, which presumably results tighter condensation better endosomal escape PEI/DNA complexes. As validation potential such linear, fully gene therapy diseases, systemic complexes short interfering RNA (siRNA) against model gene, firefly luciferase, or afforded 77% 93% suppression expression lungs, respectively. Furthermore, polyplex siRNA influenza viral nucleocapsid protein resulted 94% drop virus titers lungs influenza-infected animals.