Evaluation of the effect of vector architecture on DNA condensation and gene transfer efficiency
Evaluation of the effect of vector architecture on DNA condensation and gene transfer efficiency
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DOI：
10.1016/j.jconrel.2008.04.012
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发表时间：
2008-07-14
影响因子：
10.8
通讯作者：
Hatefi, Arash
中科院分区：
文献类型：
--
作者：
Canine, Brenda F.;Wang, Yuhua;Hatefi, Arash
本研究的目的是评估载体结构对DNA凝聚、颗粒稳定性和基因转移效率的影响。两个重组非病毒载体具有相同的氨基酸组成，但不同的架构，由赖氨酸-组氨酸（KH）的重复单位融合成纤维细胞生长因子，基因工程。在一个载体中，赖氨酸残基分散（KHKHKHKKK）（6）-FGF 2，而在另一个载体中，它们成簇（KKKHHHHKKK）（6）-FGF 2。以这种方式组织赖氨酸残基的灵感来自于自然界中存在的DNA缩合基序的序列（例如，组蛋白），其中赖氨酸残基组织成簇。这两种构建体在DNA凝聚和基因转移效率方面进行了比较。观察到在簇中具有KH单元的构建体能够将pDNA浓缩成更稳定的颗粒，
The objective of this study was to evaluate the effect of vector architecture on DNA condensation, particle stability, and gene transfer efficiency. Two recombinant non-viral vectors with the same amino acid compositions but different architectures, composed of lysine-histidine (KH) repeating units fused to fibroblast growth factor, were genetically engineered. In one vector lysine residues were dispersed (KHKHKHKHKK)(6)-FGF2, whereas in the other they were in clusters (KKKHHHHKKK)(6)-FGF2. Organization of lysine residues in this manner was inspired by the sequence of DNA condensing motifs that exist in nature (e.g., histones) where lysine residues are organized in clusters. These two constructs were compared in terms of DNA condensation and gene transfer efficiency. It was observed that the construct with KH units in clusters was able to condense pDNA into more stable particles with sizes