Efficient gene delivery by urocanic acid-modified chitosan.
Nonviral delivery systems for gene therapy have been increasingly proposed as safer alternatives to viral vectors. Chitosan is considered to be a good candidate for the gene delivery system since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic charge potential. However, the use of chitosan for gene delivery is limited due to low transfection efficiency. To enhance the transfection efficiency, water-soluble chitosan (WSC) was coupled with urocanic acid (UA) bearing imidazole ring which can play the crucial role in endosomal rupture through proton sponge mechanism. The urocanic acid-modified chitosan (UAC) was complexed with DNA, and UAC/DNA complexes were characterized. The sizes of UAC/DNA complexes under physiological condition (109-342 nm) were almost same as those of chitosan-DNA complexes. UAC also showed good DNA binding ability, high protection of DNA from nuclease attack, and low cytotoxicity. The transfection efficiency of chitosan into 293T cells was much enhanced after coupling with UA and increased with an increase of UA contents in the UAC.
Kim
Tae Hee
TH
School of Agricultural Biotechnology, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-742, South Korea.
Ihm
Jong Eun
JE
Choi
Yun Jaie
YJ
Nah
Jae Woon
JW
Cho
Chong Su
CS
D002460:Cell Line; D002686:Chitin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D014560:Urocanic Acid / Q000008:administration & dosage* / Q000737:chemistry
D002686:Chitin; D004247:DNA; D048271:Chitosan; D014560:Urocanic Acid