A review of therapeutic aptamer conjugates with emphasis on new approaches.
A review of therapeutic aptamer conjugates with emphasis on new approaches.
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DOI：
10.3390/ph6030340
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发表时间：
2013-03-19
期刊：
影响因子：
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通讯作者：
Bruno JG
中科院分区：
文献类型：
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作者：
Bruno JG
用核酸适体模拟或增强抗体同时降低成本的潜力已经促进了新的适体-蛋白质、siRNA、药物和纳米颗粒缀合物的开发。本综述的具体焦点讨论了DNA适体在其3'端共价结合到各种蛋白质，以增强体内稳定性和更长的药代动力学寿命。这些蛋白质可以包括用于调理作用的IgG的Fc尾，以及补体的第一组分（C1 q），以在脆弱阶段触发补体介导的对抗生素抗性革兰氏阴性细菌、癌细胞和可能的一些寄生虫的裂解。此外，3'蛋白加合物可以是生物毒素、酶，或者可以简单地是人血清白蛋白（HSA）或已知结合HSA的药物，从而延迟肾和其它器官清除并抑制血清核酸外切酶。在这篇综述中，作者总结了现有的治疗性适体缀合物类别，并描述了他的专利概念，即基于PCR的双链适体扩增，然后将蛋白质或其他试剂共价连接到由Taq聚合酶添加的化学脆弱的悬垂3'腺嘌呤上。适体的PCR扩增可以显著降低目前平行化学寡核苷酸合成的2，000美元/克成本，从而使得适体-3 '-蛋白质或药物缀合物的大规模生产能够更好地与昂贵的人源化单克隆抗体竞争。
The potential to emulate or enhance antibodies with nucleic acid aptamers while lowering costs has prompted development of new aptamer-protein, siRNA, drug, and nanoparticle conjugates. Specific focal points of this review discuss DNA aptamers covalently bound at their 3' ends to various proteins for enhanced stability and greater pharmacokinetic lifetimes in vivo. The proteins can include Fc tails of IgG for opsonization, and the first component of complement (C1q) to trigger complement-mediated lysis of antibiotic-resistant Gram negative bacteria, cancer cells and possibly some parasites during vulnerable stages. In addition, the 3' protein adduct may be a biotoxin, enzyme, or may simply be human serum albumin (HSA) or a drug known to bind HSA, thereby retarding kidney and other organ clearance and inhibiting serum exonucleases. In this review, the author summarizes existing therapeutic aptamer conjugate categories and describes his patented concept for PCR-based amplification of double-stranded aptamers followed by covalent attachment of proteins or other agents to the chemically vulnerable overhanging 3' adenine added by Taq polymerase. PCR amplification of aptamers could dramatically lower the current $2,000/gram cost of parallel chemical oligonucleotide synthesis, thereby enabling mass production of aptamer-3'-protein or drug conjugates to better compete against expensive humanized monoclonal antibodies.