Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs)

被引：32

作者：

Benner, Nancy L. ^{[1
]}

Near, Katherine E. ^{[1
,6
,7
]}

Bachmann, Michael H. ^{[2
,8
]}

Contag, Christopher H. ^{[2
,3
,4
,9
,10
]}

Waymouth, Robert M. ^{[1
]}

Wender, Paul A. ^{[1
,5
]}

机构：

[1] Stanford Univ, Dept Chem, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Chem & Syst Biol, Stanford, CA 94305 USA

[6] Univ Calif Berkeley, Dept Chem & Nutr Sci, 127 Morgan Hall, Berkeley, CA 94720 USA

[7] Univ Calif Berkeley, Dept Toxicol, 127 Morgan Hall, Berkeley, CA 94720 USA

[8] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA

[9] Michigan State Univ, Inst Quantitat Hlth Sci & Engn, E Lansing, MI 48824 USA

[10] Michigan State Univ, Dept Biomed Engn, E Lansing, MI 48824 USA

来源：

BIOMACROMOLECULES | 2018年 / 19卷 / 07期

基金：

美国国家科学基金会;

关键词：

RING-OPENING POLYMERIZATION; BEAUTY TRANSPOSON SYSTEM; ARGININE-RICH PEPTIDES; STABLE GENE-TRANSFER; PLASMID DNA; SLEEPING-BEAUTY; BRYOSTATIN; IN-VIVO; CELLS; EFFICIENT;

D O I：

10.1021/acs.biomac.8b00401

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Safe and effective DNA delivery systems are required to enable or enhance clinical strategies and research involving gene therapy and DNA vaccinations. To address this delivery problem, a series of charge-altering releasable transporters (CARTs) with varied lipid content were prepared and evaluated for plasmid DNA (pDNA) delivery into cultured cells. These lipid-modified CART co-oligomers were synthesized in only two steps via sequential organocatalytic ring opening polymerization of lipid-containing cyclic carbonate monomers and morpholinone monomers. Lipid variations of the CARTs substantially impacted the delivery efficiency of pDNA, with oleyl- and linoleyl-based CARTs showing enhanced performance relative to the commercial transfection agent Lipofectamine 2000 (L2000). The best-performing oleyl CART was carried forward to study stable luciferase transfection with a Sleeping Beauty (SB) transposon system. The oleyl CART outperformed the L2000 positive control with respect to stable transfection efficiency. CART-pDNA complexes represent a new DNA delivery system for research and clinical applications.

引用

页码：2812 / 2824

页数：13

共 73 条

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