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Annealing novel nucleobase-lipids with oligonucleotides or plasmid DNA based on H-bonding or π-π interaction: Assemblies and transfections
Biomaterials ( IF 12.8 ) Pub Date : 2018-06-14 , DOI: 10.1016/j.biomaterials.2018.06.012
Yuan Ma , Yuejie Zhu , Chao Wang , Delin Pan , Shuang Liu , Mengyi Yang , Zhangping Xiao , Xiantao Yang , Wenting Zhao , Xinyang Zhou , Yiding Li , Yufei Pan , Jing Sun , Shuhe Wang , Zhu Guan , Lihe Zhang , Zhenjun Yang

Lipid derivatives of nucleoside analogs have been highlighted for their potential for effective gene delivery. A novel class of nucleobase-lipids are rationally designed and readily synthesized, comprising thymine/cytosine, an ester/amide linker and an oleyl lipid. The diversity of four nucleobase-lipids termed DXBAs (DOTA, DNTA, DOCA and DNCA) is investigated. Besides, DNCA is demonstrated to be an effective neutral transfection material for nucleic acid delivery, which enbles to bind to oligonucleotides via H-bonding and π-π stacking with reduced toxicity in vitro and in vivo. Several kinds of nucleic acid drugs including aptamer, ssRNA, antisense oligonucleotide, and plasmid DNAs can be delivered by DXBAs, especially DNCA. In particular, G4-aptamer AS1411 encapsulated by DNCA exhibits cellular uptake enhancement, lysosome degradation reduction, cell apoptosis, cycle phase alteration in vitro and duration prolongation in vivo, resulting in significantly anti-proliferative activity. Our results demonstrate that DNCA is a promising transfection agent for G4-aptamers and exhibites bright application prospects in the permeation improvement of single-stranded oligonucleotides or plasmid DNA.



中文翻译:

基于H键或π-π相互作用的寡核苷酸或质粒DNA对新型核碱基-脂质进行退火:组装和转染

核苷类似物的脂质衍生物因其有效基因递送的潜力而被强调。合理设计并易于合成的新型一类核碱基-脂质,包括胸腺嘧啶/胞嘧啶,酯/酰胺连接基和油基脂质。研究了四个称为DXBA(DOTA,DNTA,DOCA和DNCA)的核碱基脂质的多样性。此外,DNCA被证明是用于核酸递送的有效转染中性材料,其通过氢键和π-πenbles结合到寡核苷酸具有降低的毒性堆叠在体外体内。DXBA(尤其是DNCA)可以递送多种核酸药物,包括适体,ssRNA,反义寡核苷酸和质粒DNA。特别地,由DNCA包封的G4-适体AS1411表现出细胞摄取增强,溶酶体降解减少,细胞凋亡,体外周期阶段改变和体内持续时间延长,从而导致显着的抗增殖活性。我们的结果表明,DNCA是一种有前途的G4适配子转染剂,在单链寡核苷酸或质粒DNA的渗透性改善中显示出广阔的应用前景。

更新日期:2018-06-14
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