Acetylation of polyethylenimine enhances gene delivery via weakened polymer/DNA interactions
Acetylation of polyethylenimine enhances gene delivery via weakened polymer/DNA interactions
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DOI：
10.1021/bm060300u
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发表时间：
2006-08-14
影响因子：
6.2
通讯作者：
Pack, Daniel W.
中科院分区：
文献类型：
--
作者：
Gabrielson, Nathan P.;Pack, Daniel W.
我们以前报道，25 kDa的，支链聚乙烯亚胺（PEI）的基因传递效率增加后乙酰化的伯胺与乙酸酐高达43%。在本工作中，我们研究了进一步提高乙酰化程度的影响，并阐明了更高的基因递送效率的来源。尽管缓冲能力降低，但随着高达57%的伯胺的乙酰化，基因递送活性继续增加（在HEK 293中高达58倍），但在更高的乙酰化程度下降低。聚合物-DNA相互作用的表征表明，乙酰化的聚合物结合不太强烈的DNA。此外，荧光共振能量转移测定显示，增加乙酰化导致复合物在细胞内以比用未修饰的PEI形成的复合物更高的程度解包。总体而言，数据表明，增加的基因递送活性可能归因于聚合物缓冲能力和聚合物/DNA相互作用强度之间的适当平衡。
We previously reported that gene delivery efficiency of 25-kDa, branched polyethylenimine (PEI) increased upon acetylation of up to 43% of the primary amines with acetic anhydride. In the present work, we investigated the effects of further increasing the degree of acetylation and elucidated the source of the higher gene delivery efficiency. Despite reduced buffering capacity, gene delivery activity continued to increase (up to 58-fold in HEK293) with acetylation of up to 57% of primary amines but decreased at higher degrees of acetylation. Characterization of polymer-DNA interactions showed that acetylated polymers bind less strongly to DNA. Further, a fluorescence resonance energy transfer assay showed that increasing acetylation causes polyplexes to unpackage inside cells to a higher degree than polyplexes formed with unmodified PEI. Overall, the data suggest that the increased gene delivery activity may be attributable to an appropriate balance between polymer buffering capacity and strength of polymer/DNA interactions.