Biodegradable polyester, poly[alpha-(4-aminobutyl)-L-glycolic acid], as a non-toxic gene carrier.
OBJECTIVE
The aim of this study was to develop a non-toxic polymeric gene carrier. For this purpose, biodegradable cationic polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) was synthesized. PAGA was designed to have ester linkage because polyesters usually show biodegradability.


METHODS
Degradation of PAGA in an aqueous solution was followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). PAGA/DNA complexes were characterized by gel electrophoresis, atomic force microscopy (AFM), dynamic light scattering (DLS). The transfection was measured by using the beta-galactosidase reporter gene.


RESULTS
PAGA was degraded in aqueous solution very quickly and the final degradation product was a monomer (L-oxylysine). Formation of self-assembling biodegradable complexes between PAGA and DNA at a charge ratio 1:1 (+/-) was confirmed by gel band shift assay and AFM. In these studies, controlled release of DNA from the complexes could be seen. The complexes showed about 2-fold higher transfection efficiency than DNA complexes of poly-L-lysine (PLL), a structural analogue of PAGA, which is the most commonly used poly-cation for gene delivery. The polymer did not show cytotoxicity, possibly because of its degradability and the biocompatibility of the monomer.


CONCLUSIONS
The use of the biodegradable poly-cation, PAGA, as a DNA condensing agent will be useful in safe gene delivery.
Lim
Y B
YB
School of Chemistry & Molecular Engineering, Seoul National University, Korea.
Han
S O
SO
Kong
H U
HU
Lee
Y
Y
Park
J S
JS
Jeong
B
B
Kim
S W
SW
D020341:Absorbable Implants; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004337:Drug Carriers; D006801:Humans; D011100:Polyglycolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000235:genetics; D014162:Transfection
D004337:Drug Carriers; C414262:poly((4-aminobutyl)glycolic acid); D011107:Polylysine; D011100:Polyglycolic Acid; D004247:DNA