Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 811-816 |
| Number of pages | 6 |
| Journal | Pharmaceutical Research |
| Volume | 17 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2000 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Organic Chemistry
- Pharmacology (medical)
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Biodegradable polyester, poly[α-(4-Aminobutyl)-L-glycolic acid], as a non-toxic gene carrier. / Lim, Yong Beom; Han, Sang Oh; Kong, Han Uk; Lee, Yah; Park, Jong Sang; Jeong, Byeongmoon; Kim, Sung Wan.
In: Pharmaceutical Research, Vol. 17, No. 7, 01.01.2000, p. 811-816.Research output: Contribution to journal › Article
TY - JOUR
T1 - Biodegradable polyester, poly[α-(4-Aminobutyl)-L-glycolic acid], as a non-toxic gene carrier
AU - Lim, Yong Beom
AU - Han, Sang Oh
AU - Kong, Han Uk
AU - Lee, Yah
AU - Park, Jong Sang
AU - Jeong, Byeongmoon
AU - Kim, Sung Wan
PY - 2000/1/1
Y1 - 2000/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033842684&partnerID=8YFLogxK
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U2 - 10.1023/A:1007552007765
DO - 10.1023/A:1007552007765
M3 - Article
C2 - 10990199
AN - SCOPUS:0033842684
VL - 17
SP - 811
EP - 816
JO - Pharmaceutical Research
JF - Pharmaceutical Research
SN - 0724-8741
IS - 7
ER -