Purpose. The aim of this study was to develop a non-toxic polymeric gene carrier. For this purpose, biodegradable cationic polymer, poly[α-(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 β-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.
Bibliographical noteFunding Information:
We acknowledge support of this work from the Brain Korea 21 program, Korea Research Foundation, Korea Science and Engineering Foundation, and Expression Genetics Inc.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Pharmaceutical Science
- Organic Chemistry
- Pharmacology (medical)