Viral capsid DNA aptamer conjugates as multivalent cell-targeting vehicles.
Viral capsid DNA aptamer conjugates as multivalent cell-targeting vehicles.
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DOI：
10.1021/ja903857f
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发表时间：
2009-08-12
影响因子：
15
通讯作者：
Francis, Matthew B.
中科院分区：
文献类型：
--
作者：
Tong, Gary J.;Hsiao, Sonny C.;Carrico, Zachary M.;Francis, Matthew B.
核酸适体作为一种方便的、可进化的靶向基团，为药物输送提供了巨大的潜力。为了将它们附着在无基因组的病毒衣壳载体的表面，一种有效的氧化偶联策略已经开发出来。该方法涉及高碘酸盐介导的苯二胺取代的寡核苷酸与安装在衣壳外表面的苯胺基团的反应。每个病毒衣壳上可以连接多达60条DNA链，而不会明显丧失碱基配对能力或蛋白质稳定性。衣壳结合特定细胞靶点的能力是通过在Jurkat T细胞上连接针对酪氨酸激酶受体的41个核苷酸序列来证明的。在衣壳内部安装荧光染料后，与对照样品相比，带有细胞靶向序列的衣壳显示出与细胞的显著结合水平。利用共聚焦显微镜进行的共定位实验表明，衣壳被内吞并运输到溶酶体进行降解。这些观察结果表明，适体标记的衣壳可以用于靶向给药，这些药物在溶酶体酸化时优先释放。
Nucleic acid aptamers offer significant potential as convenient and evolvable targeting groups for drug delivery. To attach them to the surface of a genome-free viral capsid carrier, an efficient oxidative coupling strategy has been developed. The method involves the periodate-mediated reaction of phenylene diamine substituted oligonucleotides with aniline groups installed on the outer surface of the capsid shells. Up to 60 DNA strands can be attached to each viral capsid with no apparent loss of base-pairing capabilities or protein stability. The ability of the capsids to bind specific cellular targets was demonstrated through the attachment of a 41-nucleotide sequence that targets a tyrosine kinase receptor on Jurkat T cells. After the installation of a fluorescent dye on the capsid interior, capsids bearing the cell-targeting sequence showed significant levels of binding to the cells relative to control samples. Colocalization experiments using confocal microscopy indicated that the capsids were endocytosed and trafficked to lysosomes for degradation. These observations suggest that aptamer-labeled capsids could be used for the targeted drug delivery of acid-labile prodrugs that would be preferentially released upon lysosomal acidification.
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影响因子：
3.2
作者：
Huang, Yu-Fen;Shangguan, Dihua;Liu, Haipeng;Phillips, Joseph A.;Zhang, Xiaoling;Chen, Yan;Tan, Weihong
通讯作者：
Tan, Weihong
影响因子：
10.8
作者：
Hooker, Jacob M.;Datta, Ankona;Francis, Matthew B.
通讯作者：
Francis, Matthew B.
影响因子：
15
作者：
Hooker, JM;Kovacs, EW;Francis, MB
通讯作者：
Francis, MB
影响因子：
15
作者：
Hooker, Jacob M.;Esser-Kahn, Aaron P.;Francis, Matthew B.
通讯作者：
Francis, Matthew B.
适体介导的siRNA传递。
影响因子：
14.9
作者：
Chu, Ted C.;Twu, Karen Y.;Ellington, Andrew D.;Levy, Matthew
通讯作者：
Levy, Matthew