Histidylated Lipid-modified Sendai Viral Envelopes Mediate Enhanced Membrane Fusion and Potentiate Targeted Gene Delivery*
Histidylated Lipid-modified Sendai Viral Envelopes Mediate Enhanced Membrane Fusion and Potentiate Targeted Gene Delivery*
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组酰化脂质修饰的仙台病毒包膜介导增强的膜融合并增强靶向基因传递*
DOI：
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发表时间：
2005
影响因子：
4.8
通讯作者：
D. P. Sarkar
中科院分区：
文献类型：
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作者：
S. Verma;P. Mani;N. Sharma;Anuja Krishnan;V. V. Kumar;B. S. Reddy;A. Chaudhuri;R. P. Roy;D. P. Sarkar
最近的研究表明，将单个组氨酸残基共价接枝到双链脂肪烃化合物中可以增强其内体破坏性能，从而产生良好的DNA转染系统。因此，通过在各种阳离子聚合物的分子结构中使用内核体破坏多组氨酸功能，可以显著提高基因传递效率。为了利用这一独特的特性，我们将l -组氨酸（N，N-二- N-十六烷基胺）乙基酰胺（LH）掺入仅含有融合蛋白的肝细胞特异性仙台病毒体的膜中（f -病毒体（生产靶基因的过程（Sarkar， D. P., Ramani， K., Bora， R. S., Kumar， M., and Tyagi， S. K.（1997年11月4日）美国专利5,683,866）））。在与靶细胞膜融合方面，这种修饰的病毒体包膜的活性增加了4倍（p < 0.001）。另一方面，重组流感病毒和水疱性口炎病毒包膜中LH的存在未能增强刺突糖蛋白诱导的膜与宿主细胞膜的融合。F-病毒体的环状二色性和有限蛋白水解实验表明，LH的存在导致F蛋白的构象改变。LH诱导膜融合增加的分子机制已经在F蛋白的融合能力构象变化的基础上得到了解决。这种融合的增强导致了一个高效的基因传递系统特异性的肝细胞在培养和整个动物。
Recent studies have demonstrated that covalent grafting of a single histidine residue into a twin-chain aliphatic hydrocarbon compound enhances its endosome-disrupting properties and thereby generates an excellent DNA transfection system. Significant increase in gene delivery efficiencies has thus been obtained by using endosome-disrupting multiple histidine functionalities in the molecular architecture of various cationic polymers. To take advantage of this unique feature, we have incorporated L-histidine (N,N-di-n-hexadecylamine) ethylamide (LH) in the membrane of hepatocyte-specific Sendai virosomes containing only the fusion protein (F-virosomes (Process for Producing a Targeted Gene (Sarkar, D. P., Ramani, K., Bora, R. S., Kumar, M., and Tyagi, S. K. (November 4, 1997) U. S. Patent 5,683,866))). Such LH-modified virosomal envelopes were four times more (p < 0.001) active in terms of fusion with its target cell membrane. On the other hand, the presence of LH in reconstituted influenza and vesicular stomatitis virus envelopes failed to enhance spike glycoprotein-induced membrane fusion with host cell membrane. Circular dichroism and limited proteolysis experiments with F-virosomes indicated that the presence of LH leads to conformational changes in the F protein. The molecular mechanism associated with the increased membrane fusion induced by LH has been addressed in the light of fusion-competent conformational change in F protein. Such enhancement of fusion resulted in a highly efficient gene delivery system specific for liver cells in culture and in whole animals.
仙台病毒融合蛋白（f）的激活涉及随着新疏水区域的暴露而发生的构象变化。
DOI：
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发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hsu,M;Scheid,A;Choppin,PW
通讯作者：
Choppin,PW
DOI：
10.1073/pnas.260499197
发表时间：
2000-12-19
影响因子：
11.1
作者：
Zhao, X;Singh, M;Kim, PS
通讯作者：
Kim, PS