Lipitoids - novel cationic lipids for cellular delivery of plasmid DNA in vitro

被引：74

作者：

Huang, CY ^{[1
]}

Uno, T ^{[1
]}

Murphy, JE ^{[1
]}

Lee, S ^{[1
]}

Hamer, JD ^{[1
]}

Escobedo, JA ^{[1
]}

Cohen, FE ^{[1
]}

Radhakrishnan, R ^{[1
]}

Dwarki, V ^{[1
]}

Zuckermann, RN ^{[1
]}

机构：

[1] Chiron Corp, Chiron Technol, Emeryville, CA 94608 USA

来源：

CHEMISTRY & BIOLOGY | 1998年 / 5卷 / 06期

关键词：

cationic lipid; gene transfer; lipitoid; nonviral gene therapy; peptoid;

D O I：

10.1016/S1074-5521(98)90173-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Although synthetic nonviral vectors hold promise for the delivery of plasmid DNA, their gene-transfer efficiencies are far from matching those of viruses. To systematically investigate the structure-activity relationship of cationic lipids, a small library of cationic lipid-peptoid conjugates (lipitoids) was synthesized. The compounds were evaluated for their ability to form complexes with plasmid DNA and to mediate DNA transfer in vitro. Results: Lipid-peptoid conjugates were conveniently prepared in high yield using solid-phase synthesis. Several lipitoids condensed plasmid DNA int 100 nm spherical particles and protected the DNA from DNase digestion, A subset of lipitoids with a repeated (aminoethyl, neutral, neutral) sidechain trimer motif conjugated with dimyristoyl phosphatidyl-ethanolamine (DMPE) mediate DNA transfer with high efficiency. Conclusions: Automated solid-phase synthesis of cationic lipids allowed the rapid synthesis of a diverse set of transfection reagents. The most active compound DMPE-(Nae-Nmpe-Nmpe)(3) (Nae, N-aminoethyl glycine; Nmpe, N-p-methoxyphenethyl-glycine) is more efficient than lipofectin or DMRIE-C (two commercial cationic lipid transfection reagents) and is active in the presence and absence of serum. The activity in the presence of serum suggests potent at for applications in vivo.

引用

页码：345 / 354

页数：10

共 40 条

[1] PROSPECTS FOR HUMAN-GENE THERAPY [J].