Versatile peptide dendrimers for nucleic acid delivery

被引:49
作者
Bayele, HK
Sakthivel, T
O'Donell, M
Pasi, KJ
Wilderspin, AF
Lee, CA
Toth, I
Florence, AT
机构
[1] Univ London, Sch Pharm, London WC1N 1AX, England
[2] UCL, Dept Haematol, London NW3 2PF, England
关键词
dendrimer; gene delivery; vector; transfection; lipidic peptide; versatile;
D O I
10.1002/jps.20230
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Dendrimers are nonviral vectors that have attracted interest on account of a number of features. They are structurally versatile because their size, shape, and surface charge can be selectively altered. Here we examine the functions of a new family of composite dendrimers that were synthesized with lipidic amino acid cores. These dendrimers are bifunctional because they are characterized by positively charged (lysine) modules for interaction with nucleic acids and neutral lipidic moieties for membrane lipid-bilayer transit. We assessed their structure-function correlations by a combination of molecular and biophysical techniques. Our assessment revealed an unexpected pleitropy of functions subserved by these vectors that included plasmid and oligonucleotide delivery. We also generated a firefly luciferase cell line in which we could modulate luciferase activity by RNA interference. We found that these vectors could also mediate RNA suppression of luciferase expression by delivering double-stranded luciferase transcripts generated in vitro. The structural uniqueness of these lipidic peptide dendrimers coupled with their ease and specificity of assembly and the versatility in their choice of cargo, puts them in a new category of macromolecule carriers. These vectors, therefore, have potential applications as epigenetic modifiers of gene function. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.
引用
收藏
页码:446 / 457
页数:12
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