Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs)
Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs)
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DOI：
10.1021/acs.biomac.8b00401
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发表时间：
2018-07-01
影响因子：
6.2
通讯作者：
Wender, Paul A.
中科院分区：
文献类型：
--
作者：
Benner, Nancy L.;Near, Katherine E.;Wender, Paul A.
需要安全有效的DNA递送系统来实现或加强涉及基因治疗和DNA疫苗接种的临床策略和研究。为了解决这一递送问题，制备了一系列具有不同脂质含量的电荷改变可释放转运体（CART），并评估了质粒DNA（pDNA）递送到培养细胞中。这些脂质改性的CART共低聚物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在仅两个步骤中合成。CART的脂质变化显著影响pDNA的递送效率，其中基于油基和亚油基的CART显示出相对于商业转染剂Lipofectamine 2000（L2000）增强的性能。将表现最好的油基CART用于研究用睡美人（SB）转座子系统的稳定荧光素酶转染。油基CART在稳定转染效率方面优于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。
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.