The Role of Formamidine Groups in Dextran Based Nonviral Vectors for Gene Delivery on Their Physicochemical and Biological Characteristics,Macromolecular Bioscience

当前位置： X-MOL 学术 › Macromol. Biosci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

The Role of Formamidine Groups in Dextran Based Nonviral Vectors for Gene Delivery on Their Physicochemical and Biological Characteristics
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2020-10-07 , DOI: 10.1002/mabi.202000220
Dagmar Fischer _{1,

2} , Niels Dusek ₁ , Konrad Hotzel ₃ , Thomas Heinze _{2,

3}

Affiliation

Dextran‐formamidine esters (dextran‐N‐[(dimethylamino)methylene]‐β‐alanine ester) with different degrees of substitution (0.45–0.92) are synthesized in an one‐pot reaction. Dextran (Mw 60 000 g mol⁻¹) is allowed to react with unprotected beta‐alanine and iminium chloride and investigated regarding the potential as gene delivery system for the transfer of plasmid DNA. With degrees of substitution ≥ 0.63 improved DNA binding with formation of enzymatically stable complexes of about 130–160 nm with negative surface charges are obtained. These physicochemical characteristics correlated with increasing transfection rates in CHO‐K1 cells determined by a luciferase reporter gene assay in dependency of the number of formamidine residues, N/P ratios and amount of DNA. The role of the number of formamidine groups is also highlighted by in vitro cyto‐ and hemotoxicity tests under the chosen conditions. These results indicate that dextran‐formamidine esters are a very promising material for the safe and efficient gene delivery.

中文翻译：

甲脒基团在用于基因递送的基于葡聚糖的非病毒载体中对其理化和生物学特性的作用

具有不同取代度（0.45-0.92）的葡聚糖-甲脒酯（葡聚糖-N -[（二甲氨基）亚甲基]-β-丙氨酸酯）是在一锅反应中合成的。葡聚糖 (Mw 60 000 g mol ^-1) 与未受保护的 β-丙氨酸和氯化亚胺反应，并研究其作为质粒 DNA 转移的基因传递系统的潜力。取代度≥ 0.63 时，DNA 结合得到改善，形成约 130–160 nm 的酶稳定复合物，表面带负电荷。这些物理化学特征与 CHO-K1 细胞中转染率的增加相关，通过荧光素酶报告基因检测，依赖于甲脒残基的数量、N/P 比和 DNA 量。所选条件下的体外细胞毒性和血液毒性试验也强调了甲脒基团数量的作用。这些结果表明，葡聚糖-甲脒酯是一种非常有前途的安全有效基因传递材料。

更新日期：2020-10-07

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11