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Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs)
Biomacromolecules ( IF 6.2 ) Pub Date : 2018-05-04 00:00:00 , DOI: 10.1021/acs.biomac.8b00401
Nancy L. Benner , Katherine E. Near , Michael H. Bachmann , Christopher H. Contag , Robert M. Waymouth , Paul A. Wender

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.

中文翻译:

脂质修饰的电荷改变型可释放转运蛋白(CART)实现了功能性DNA的传递。

需要安全有效的DNA传递系统来启用或增强涉及基因治疗和DNA疫苗接种的临床策略和研究。为了解决该递送问题,制备了一系列具有可变脂质含量的可改变电荷的可释放转运蛋白(CART),并评估了质粒DNA(pDNA)递送至培养细胞中的能力。这些脂质修饰的CART共聚体仅通过两个步骤就可以通过含脂质的环状碳酸酯单体和吗啉酮单体的连续有机催化开环聚合反应来合成。CART的脂质变化极大地影响了pDNA的传递效率,相对于商业转染剂Lipofectamine 2000(L2000),基于油基和亚油基的CART表现出更高的性能。睡美人SB)转座子系统。就稳定的转染效率而言,油基CART优于L2000阳性对照。CART-pDNA复合物代表了一种用于研究和临床应用的新的DNA递送系统。
更新日期:2018-05-04
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