Bile acid-oligopeptide conjugates interact with DNA and facilitate transfection

被引:24
作者
Kish, Phillip E.
Tsume, Yasuhiro
Kijek, Paul
Lanigan, Thomas M.
Hilfinger, John M.
Roessler, Blake J.
机构
[1] TSRL Inc, Ann Arbor, MI 48108 USA
[2] Univ Michigan, Ctr Gene Therapy, Dept Internal Med, Ann Arbor, MI 48109 USA
关键词
bile acid; cholesterol; gene therapy; polyarginine; plasmid; nanoparticles; silica;
D O I
10.1021/mp060025q
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Bile acids conjugated to oligoarginine-containing peptides (BACs) form complexes with DNA based on the electrostatic interactions between negatively charged phosphate groups of the nucleic acid and the positively charged side chain guanidinium groups of the oligoarginine in the BACs. Charge neutralization of both components and subsequent increases of the net positive charge of the complex combined with the water-soluble lipophilic nature of the bile acid results in changes in the physicochemistry and biological properties of the complexes. We have examined the relationship of a series of 13 BACs on their interaction with circular plasmid DNA (pDNA). The formation of soluble, low-density and insoluble, high-density complexes was analyzed using several methods. The formation of high-density complexes was dependent on the DNA concentration, and was enhanced by increasing the BAC to pDNA charge ratio. Several of the BAC:pDNA complexes demonstrated exclusion of the DNA-intercalator Hoechst 33258 from pDNA, and were also protected from DNase activity. Several BAC conjugates interacted with pDNA to form nanometer-sized particles suitable for cell transfection in vitro. Five of the 13 BACs were transfection competent as single agents, and 11 of the 13 BACs showed enhancement of transfection in combination with DOPE containing liposomes or silica nanoparticles.
引用
收藏
页码:95 / 103
页数:9
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