RRC ID 42017
Author Okuda T, Sugiyama A, Niidome T, Aoyagi H.
Title Characters of dendritic poly(L-lysine) analogues with the terminal lysines replaced with arginines and histidines as gene carriers in vitro.
Journal Biomaterials
Abstract The development of a non-viral gene delivery system into cells is an important key to realize the safe delivery of therapeutic genes without the side effects often pointed out for viral vectors. We have shown that dendritic poly(L-lysine) of the 6th generation (KG6) shows high transfection efficiency into several cultivated cells with low cytotoxicity. Here, to investigate the effect of substituting terminal cationic groups on the gene delivery into cells, we synthesized KGR6 and KGH6, in which terminal amino acids were replaced by arginines and histidines, respectively. DNA-binding analysis showed that KGR6 could bind to the plasmid DNA as strongly as KG6, whereas KGH6 showed decreased binding ability. KGR6 showed 3- to 12-fold higher transfection efficiency into several cultivated cells than KG6. In contrast, KGH6 showed no transfection efficiency. However, once KGH6 was mixed with the DNA under acidic conditions (pH 5.0), DNA-complexes were formed and they showed high transfection efficiency compared to that in KG6-mediated transfection. DNA-complexes of KGH6 formed under acidic conditions were 1-2 microm and spherical, and relatively stable under neutral conditions. The size and spherical shape of the complexes were the same as those of KG6. The unique character of KGH6 will be one of the basic and valuable tools which will enable us to construct a functional gene transfection system in vitro and in vivo.
Volume 25(3)
Pages 537-44
Published 2004-2-1
DOI 10.1016/s0142-9612(03)00542-8
PII S0142961203005428
PMID 14585703
MeSH Animals Arginine / chemistry* CHO Cells COS Cells Cations Cricetinae DNA / chemistry Dendrites / metabolism* Electrophoresis, Agar Gel Gene Transfer Techniques* Genetic Vectors HeLa Cells Histidine / chemistry* Humans Hydrogen-Ion Concentration Lysine / chemistry* Microscopy, Fluorescence Models, Biological Models, Chemical Peptides / chemistry Plasmids / metabolism Polylysine / chemistry* Protein Binding Temperature Transfection
IF 10.273
Times Cited 141
Human and Animal Cells