Biodegradable polyester, poly[alpha-(4 aminobutyl)-L-glycolic acid], as a non-toxic gene carrier

Purpose. The aim of this study was to develop a non-toxic polymeric gene ca rrier For this purpose, biodegradable cationic polymer, poly[alpha-(4-amino butyl)-L-glycolic acid] (PAGA) was synthesized. PAGA was designed to have e ster 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 (MALD I-TOF MS). PAGA/DNA complexes were characterized by gel electrophoresis, at omic force microscopy (AFM), dynamic light scattering (DLS). The transfecti on was measured by using the: beta-galactosidase reporter gene. Results. PAGA was degraded in aqueous solution very quickly and the final d egradation product was a monomer (L-oxylysine). Formation of self-assemblin g 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 abou t 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 conde nsing agent will be useful in safe gene delivery.