Biodegradable, endosome disruptive, and cationic network-type polymer as a highly efficient and nontoxic gene delivery carrier.
The success of gene therapy is largely dependent on the delivery vector system. Efficient transfection and nontoxicity are two of the most important requirements of an ideal gene delivery vector. To generate both an efficient and nontoxic vector, we rationally constructed polymeric vectors to have simultaneous multiple functions, i.e., controlled degradation, an endosome disruptive function, and positive charges. Remarkably, the transfection efficiency of network poly(amino ester) (n-PAE) synthesized in this manner was comparable to that of polyethylenimine (PEI), one of the most efficient polymeric gene delivery vectors reported to date. However, there was a marked difference in cytotoxicity between the polymers. The majority of PEI-transfected cells were granulated and dead, whereas most of the cells transfected with n-PAE were viable and healthy. Successive events of efficient endosome escape of n-PAE/DNA polyplex and n-PAE biodegradation should result in high transfection efficiency and favorable cell viability response. The n-PAE-mediated transfection was also very efficient in the presence of serum. These data show that the approach we applied is a very appropriate way of making an ideal gene delivery carrier.
Lim
Yong-beom
YB
School of Chemistry & Molecular Engineering, Seoul National University, Seoul 151-742, Korea.
Kim
Seon-mi
SM
Suh
Hearan
H
Park
Jong-sang
JS
D001673:Biodegradation, Environmental; D002470:Cell Survival / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010957:Plasmids / Q000008:administration & dosage / Q000493:pharmacokinetics; D011073:Polyamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D000071228:Polyelectrolytes; D011091:Polyesters / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D014162:Transfection / Q000379:methods* / Q000592:standards; D014407:Tumor Cells, Cultured
D008156:Luciferases; D011073:Polyamines; D000071228:Polyelectrolytes; D011091:Polyesters