PEG grafted polylysine with fusogenic peptide for gene delivery: high transfection efficiency with low cytotoxicity.
For efficient gene delivery into cells, a new formulation method based on using polyethylene glycol (PEG) grafted poly(L-lysine) (PLL) and a fusogenic peptide is presented in this study. First, PEG grafted PLL (PEG-g-PLL) was complexed with DNA by controlling the polymer/DNA ratio to form negatively charged nano-particulate complexes. A positively charged fusogenic peptide, KALA, was then coated by ionic interaction onto the surface of polymer/DNA complexes to make net positively charged KALA/polymer/DNA complexes. The use of PEG-g-PLL for KALA coating significantly suppressed the aggregation of complexes due to steric stabilization effect of PEG present on the surface, while the use of PLL alone induced severe aggregation of the complexes via KALA mediated inter-particulate cross-linking. For PEG-g-PLL/DNA complexes, enhanced transfection efficiency was observed with increasing amount of KALA. This suggests that maintaining the size of DNA/polymer complexes after KALA coating plays an important role in gene transfection. KALA/DNA/PEG-g-PLL complexes exhibited lower cytotoxicity compared with other polymer/DNA complexes.
Lee
Haeshin
H
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yusong-gu, 305-701, Taejon, South Korea.
Jeong
Ji Hoon
JH
Park
Tae Gwan
TG
D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D010455:Peptides / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000633:toxicity; D011107:Polylysine / Q000494:pharmacology* / Q000633:toxicity; D012997:Solvents / Q000494:pharmacology / Q000633:toxicity; D014162:Transfection / Q000379:methods*
D004268:DNA-Binding Proteins; C105114:KALA amphipathic peptide; D010455:Peptides; D012997:Solvents; D011107:Polylysine; D011092:Polyethylene Glycols