Authors: Rohidas B. Arote, Tae Hee Kim, You Kyoung Kim, Dhananjay Jere, Hu Lin Jiang, In Young Park, Myung Haing Cho, Jae Woon Nah, Chong Su Cho
Abstract: Novel, biodegradable poly(ester amine)s (PEAs) were synthesized using hydrophobic
polycaprolactone diacrylate (PCLDA) and highly cationic polyethylenimine (PEI). This novel gene
carrier can form stable DNA complexes with particle sizes around 200 nm, and showing excellent
transfection efficiency and relatively low cytotoxicity compared with PEI 25K. Effect of
hydrophobicity on transfection efficiency and cytotoxicity was profound and was relatively
important parameter for the success of gene delivery.
453
Authors: You Kyoung Kim, In Kyu Park, Hu Lin Jiang, Rohidas B. Arote, Hwan Jeong Jeong, Eun Mi Kim, Myung Haing Cho, Hee Seung Bom, Chong Su Cho
Abstract: Polypropylenimine (PPI) dendrimers have been used by many researchers as gene
delivery carriers due to their high functionality. Glucose as a kind of carbohydrate is biocompatible
and hydrophilic. In this study, we synthesized glucosylated PPI (G-PPI) dendrimers to reduce
cytotoxicity. Glucose substitution of G-PPI dendrimers was determined by the sulfuric acid micromethod.
The G-PPI dendrimer was complexed with plasmid DNA in various N/P ratios, and the
complex was characterized. G-PPI dendrimers showed good DNA binding ability and high
protection of DNA from nuclease attack. The G-PPI dendrimer had low cytotoxicity compared to
PPI dendrimer by cytotoxicity assay. Also, transfection efficiency was influenced by glucosylation
degree and the transfection efficiency for the G-PPI-5 was slightly higher than that of PPI
dendrimer in HeLa cell line.
457
Authors: Tae Hee Kim, Hua Jin, Hyun Woo Kim, Myung Haing Cho, Jae Woon Nah, Chong Su Cho
Abstract: The key strategy for the advancement of gene therapy is the development of an efficient
targeted gene delivery system into cells. The targeted gene delivery system is especially important in
non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the
possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been
considered to be a good candidate for gene delivery system, since it is already known as a
biocompatible, biodegradable, and low toxic material with high cationic potential. However, low
specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In
this study, we focused on the chemical modification of chitosan for enhancement of cell specificity
and transfection efficiency. Also, the potential of clinical application was investigated.
449
Authors: Dhananjay Jere, Tae Hee Kim, Rohidas B. Arote, Hu Lin Jiang, Myung Haing Cho, Jae Woon Nah, Chong Su Cho
Abstract: Vectors are vital aspect of gene delivery system which decides the success of gene
therapy. Efficient transfection with minimum or no toxicity, are two principal aims of any gene
delivery system. In this our study, we rationally developed biodegradable water soluble poly(ßamino
ester) (PAE) based on spermine (SPR) and poly (ethylene glycol) (PEG), by Michael-type
addition reaction and further studied for its potential as a gene carrier. Confirmation of synthesized
PAE was done by proton NMR spectroscopy. In gel retardation assay, the PAEs have shown good
DNA binding ability over wide range of polyplexes. The addition of PEG over SPR resulted in a
novel PAE with higher degree of safety and transfection efficiency as compared with
polyethylenimine 25K (PEI) when studied in 293T human kidney carcinoma cells.
425
Authors: Tae Hee Kim, Jin Hua, Hyun Woo Kim, Myung Haing Cho, Jae Woon Nah, Yun Jaie Choi, Chong Su Cho
Abstract: The development of an efficient targeted gene delivery system into cells is an important
strategy for the advancement of gene therapy. The targeted gene delivery system is especially
important in non-viral gene transfer which shows the relative low transfection efficiency. And it also
opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been
considered to be a good candidate for gene delivery system, since it is already known as a
biocompatible, biodegradable, and low toxic material with high cationic potential. However, low
specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In
this study, we focused on the chemical modification of chitosan for enhancement of cell specificity
and transfection efficiency.
641