Abstract
The dendritic graft copolymers (PAX) consisting of a poly(L-lysine) (PLL) main chain and grafts of arabinogalactan (AG) were prepared as a liver cell-specific DNA carrier. The copolymers were successfully prepared by reductive amination reaction between a reductive end of AG and ε-amino groups of PLL using NaBH3CN as a catalyst. The fractionation of a low molecular weight fraction (Mn = 25 kDa) from a crude AG (Mn = 33 kDa) was essential for the reaction to proceed. The resulting copolymers were isolated by ultrafiltration from unreacted AG and characterized by 1H NMR and gel permeation chromatography equipped with a multiangle laser light scattering detector (GPC-MALLS). The binding and internalization of DNA to hepatoma cells, HepG2, were considerably enhanced by complexing DNA with PAX copolymers. The interactions between PAX/DNA complexes and HepG2 cells were thoroughly inhibited in the presence of a competitor to asialoglycoprotein receptors (ASGP-R), indicating high specificity of the complex to ASGP-R. Furthermore, the PAX copolymers allowed the expression of the reporter gene. Our results reveal that the PAX copolymers may provide a new research tool for cell-specific gene delivery and eventually enhance gene-therapy technology.
| Original language | English |
|---|---|
| Pages (from-to) | 353-370 |
| Number of pages | 18 |
| Journal | Preparative Biochemistry and Biotechnology |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jan 1 1999 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Biochemistry
Cite this
Preparation of dendritic graft copolymer consisting of poly-(L-lysine) and arabinogalactan as a hepatocyte specific DNA carrier. / Park, Jeong Ung; Ishihara, Tsutomu; Kano, Arihiro; Akaike, Toshihiro; Maruyama, Atsushi.
In: Preparative Biochemistry and Biotechnology, Vol. 29, No. 4, 01.01.1999, p. 353-370.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Preparation of dendritic graft copolymer consisting of poly-(L-lysine) and arabinogalactan as a hepatocyte specific DNA carrier
AU - Park, Jeong Ung
AU - Ishihara, Tsutomu
AU - Kano, Arihiro
AU - Akaike, Toshihiro
AU - Maruyama, Atsushi
PY - 1999/1/1
Y1 - 1999/1/1
N2 - The dendritic graft copolymers (PAX) consisting of a poly(L-lysine) (PLL) main chain and grafts of arabinogalactan (AG) were prepared as a liver cell-specific DNA carrier. The copolymers were successfully prepared by reductive amination reaction between a reductive end of AG and ε-amino groups of PLL using NaBH3CN as a catalyst. The fractionation of a low molecular weight fraction (Mn = 25 kDa) from a crude AG (Mn = 33 kDa) was essential for the reaction to proceed. The resulting copolymers were isolated by ultrafiltration from unreacted AG and characterized by 1H NMR and gel permeation chromatography equipped with a multiangle laser light scattering detector (GPC-MALLS). The binding and internalization of DNA to hepatoma cells, HepG2, were considerably enhanced by complexing DNA with PAX copolymers. The interactions between PAX/DNA complexes and HepG2 cells were thoroughly inhibited in the presence of a competitor to asialoglycoprotein receptors (ASGP-R), indicating high specificity of the complex to ASGP-R. Furthermore, the PAX copolymers allowed the expression of the reporter gene. Our results reveal that the PAX copolymers may provide a new research tool for cell-specific gene delivery and eventually enhance gene-therapy technology.
AB - The dendritic graft copolymers (PAX) consisting of a poly(L-lysine) (PLL) main chain and grafts of arabinogalactan (AG) were prepared as a liver cell-specific DNA carrier. The copolymers were successfully prepared by reductive amination reaction between a reductive end of AG and ε-amino groups of PLL using NaBH3CN as a catalyst. The fractionation of a low molecular weight fraction (Mn = 25 kDa) from a crude AG (Mn = 33 kDa) was essential for the reaction to proceed. The resulting copolymers were isolated by ultrafiltration from unreacted AG and characterized by 1H NMR and gel permeation chromatography equipped with a multiangle laser light scattering detector (GPC-MALLS). The binding and internalization of DNA to hepatoma cells, HepG2, were considerably enhanced by complexing DNA with PAX copolymers. The interactions between PAX/DNA complexes and HepG2 cells were thoroughly inhibited in the presence of a competitor to asialoglycoprotein receptors (ASGP-R), indicating high specificity of the complex to ASGP-R. Furthermore, the PAX copolymers allowed the expression of the reporter gene. Our results reveal that the PAX copolymers may provide a new research tool for cell-specific gene delivery and eventually enhance gene-therapy technology.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033230550&partnerID=8YFLogxK
U2 - 10.1080/10826069908544934
DO - 10.1080/10826069908544934
M3 - Article
C2 - 10548252
AN - SCOPUS:0033230550
VL - 29
SP - 353
EP - 370
JO - Preparative Biochemistry and Biotechnology
JF - Preparative Biochemistry and Biotechnology
SN - 1082-6068
IS - 4
ER -