DNA-polycation nanospheres as non-viral gene delivery vehicles

DNA-polycation nanospheres as non-viral gene delivery vehicles
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DOI:
10.1016/s0168-3659(97)00252-6
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发表时间:
1998-04-30
影响因子:
10.8
通讯作者:
August, JT
August, JT
中科院分区:
医学1区
文献类型:
--
作者:
Leong, KW;Mao, HQ;August, JT

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通过盐诱导 cDNA 和聚阳离子(如明胶和壳聚糖)复合凝聚合成的纳米球作为基因递送载体进行了评估。尺寸范围为200-750 nm的DNA纳米球可以转染多种细胞系。尽管纳米球的转染效率通常低于细胞培养中 lipofectamine 和磷酸钙对照的转染效率,但 BALB/c 小鼠肌肉中的 β-gal 表达比裸 DNA 和 lipofectamine 复合物所实现的更高且更持久。该基因递送系统具有几个吸引人的特点:(1)配体可以与纳米球缀合,用于靶向或刺激受体介导的内吞作用; (2)可以掺入溶酶体溶解剂以减少内体和溶酶体区室中DNA的降解; (3)可以共封装其他生物活性剂或多个质粒; (4)由于聚合物基质防止血清核酸酶降解,可以提高DNA的生物利用度; (5)纳米球可以冻干保存而不损失生物活性。 (C) 1998 Elsevier Science B.V.
Nanospheres synthesized by salt-induced complex coacervation of cDNA and polycations such as gelatin and chitosan were evaluated as gene delivery vehicles. DNA-nanospheres in the size range of 200-750 nm could transfect a variety of cell lines. Although the transfection efficiency of the nanospheres was typically lower han that of lipofectamine and calcium phosphate controls in cell culture, the beta-gal expression in muscle of BALB/c mice was higher and more sustained than that achieved by naked DNA and lipofectamine complexes. This gene delivery system has several attractive features: (1) ligands can be conjugated to the nanosphere for targeting or stimulating receptor-mediated endocytosis; (2) lysosomolytic agents can be incorporated to reduce degradation of the DNA in the endosomal and lysosomal compartments; (3) other bioactive agents or multiple plasmids can be co-encapsulated; (4) bioavailability of the DNA can be improved because of protection from serum nuclease degradation by the polymeric matrix; (5) the nanosphere can be lyophilized for storage without loss of bioactivity. (C) 1998 Elsevier Science B.V.