Structural advantage of dendritic poly(l-lysine) for gene delivery into cells

Masato Yamagata, Takahito Kawano, Kouhei Shiba, Takeshi Mori, Yoshiki Katayama, Takuro Niidome

研究成果: ジャーナルへの寄稿記事

113 引用 (Scopus)

抄録

This study aimed to investigate the relationships between structures of gene carrier molecules and their activities for gene delivery into cells. We compared 2 types of poly(l-lysine) as carriers, that is, dendritic poly(l-lysine) (KG6) and linear poly(l-lysine) (PLL). KG6 formed a neutral DNA complex, and its DNA compaction level was weaker than that of PLL. The amount of DNA binding and uptake into cells mediated by PLL was 4-fold higher than that with KG6. However, KG6-mediated gene expression was 100-fold higher than that by PLL. Since pKa values of terminal amines of KG6 were lowered even though small amounts of DNA were internalized into cells, sufficient DNA amounts for effective gene expression escaped to the cytosol due to the proton sponge effect in the endosome. In addition, weakly compacted DNA with KG6 was advantageous in accessing RNA polymerase in the cell nucleus. On the other hand, PLL did not show the proton sponge effect in the endosome and resulted in strong compaction of DNA. Even though large DNA amounts were internalized into cells, most of the DNA would not take part in gene expression systems in the nucleus. Amount of induced cytokine production after intravenous injection of DNA complexes with KG6 and PLL was low, and was similar to the case when DNA was injected alone. Therefore, no significant difference in effects on cytokine production was observed between KG6 and PLL.

元の言語英語
ページ(範囲)526-532
ページ数7
ジャーナルBioorganic and Medicinal Chemistry
15
発行部数1
DOI
出版物ステータス出版済み - 1 1 2007

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Lysine
Genes
Phase locked loops
DNA
Gene expression
Endosomes
Porifera
Gene Expression
Protons
Compaction
Cytokines
DNA-Directed RNA Polymerases
Cell Nucleus
Intravenous Injections
Cytosol
Amines
Cells
Molecules

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

これを引用

Structural advantage of dendritic poly(l-lysine) for gene delivery into cells. / Yamagata, Masato; Kawano, Takahito; Shiba, Kouhei; Mori, Takeshi; Katayama, Yoshiki; Niidome, Takuro.

:: Bioorganic and Medicinal Chemistry, 巻 15, 番号 1, 01.01.2007, p. 526-532.

研究成果: ジャーナルへの寄稿記事

Yamagata, Masato ; Kawano, Takahito ; Shiba, Kouhei ; Mori, Takeshi ; Katayama, Yoshiki ; Niidome, Takuro. / Structural advantage of dendritic poly(l-lysine) for gene delivery into cells. :: Bioorganic and Medicinal Chemistry. 2007 ; 巻 15, 番号 1. pp. 526-532.
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