Integrin receptor-targeted transfer peptides for efficient delivery of antisense oligodeoxynucleotides

被引:22
作者
Bachmann, AS
Surovoy, A
Jung, G
Moelling, K
机构
[1] Univ Zurich, Inst Med Virol, CH-8028 Zurich, Switzerland
[2] Univ Tubingen, Inst Organ Chem, D-72076 Tubingen, Germany
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 1998年 / 76卷 / 02期
关键词
c-Myb antisense oligodeoxynucleotides; cell proliferation; HIV-1; integrin receptors; transfer peptides;
D O I
10.1007/s001090050200
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Integrin receptor-targeted transfer of oligodeoxynucleotides (ODNs) by small synthetic peptides was used for improving delivery of antisense ODNs. An 18-mer phosphodiester bond containing ODN complementary to c-myb-encoded mRNA was complexed with several transfer peptides, containing as their parts two modules: (a) an RGD-motif as targeting sequence for integrin receptor and (b) nucleocapsid protein (NCp) 7 of HIV-1 or NCp7-derived peptides for complex formation with the ODNs. The amount of antisense ODN required for the inhibition of proliferation of human myeloid cell line HL-60 in vitro can be more than 50-fold reduced by complexing with transfer peptides. The efficiency of antisense delivery was increased by multimerization of the targeting sequence for the integrin receptor. Competition with integrin peptide abolished the effect, indicating that the integrin receptor is indeed responsible for the reaction.
引用
收藏
页码:126 / 132
页数:7
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