Cytokine aptamers as therapeutic and diagnostic agents.
- Author:
Xin-Rui YAN
1
;
Xu-Wen GAO
;
Zhi-Qing ZHANG
Author Information
1. State Key Laboratory of Molecular Virology and Genetic Engineering, Institute of Virology, China Center for Disease Control and Prevention, Beijing 100052, China.
- Publication Type:Journal Article
- MeSH:
Cytokines;
antagonists & inhibitors;
High-Throughput Screening Assays;
Humans;
Oligonucleotides;
therapeutic use;
SELEX Aptamer Technique;
Vascular Endothelial Growth Factor A;
antagonists & inhibitors
- From:
Chinese Journal of Biotechnology
2004;20(4):627-632
- CountryChina
- Language:Chinese
-
Abstract:
Aptamers are oligonucleotides derived from an in vitro evolution process called SELEX (Systematic Evolution of Ligands by Exponential Enrichment). Aptamers specially binding to targets could recognize and inhibit the function of targets. Using this method, many powerful antagonists of cytokines have been found. In order for these antagonists to work in animal models of disease and in humans, it is necessary to modify the aptamers. First of all, 2'-F, 2'-NH2 and 2'-CH3O modifications of nucleoside triphosphates could prolong half-lives in blood. Aptamers can be kept in the circulation from hours to days by conjugating them to higher molecular weight vehicles. After modified, conjugated aptamers are injected into animals, they inhibit physiological functions known to be associated with their target cytokines. Exhibiting binding characteristics comparable to or even better than monoclonal antibodies, these ligands can be used as detection probes, highly efficient inhibitors of protein function or specific competitors in high-throughput screening (HTS) assays. Recently several aptamers of cytokines have been characterized. Some of them have been used as diagnostic agent for the detection of target cytokines. The first aptamer that has proceeded to phase II clinical studies is NX-1838, an injectable angiogenesis inhibitor that can be potentially used to treat macular degeneration-induced blindness. Aptamers will be versatile tools that can greatly enhance the efficiency of modern diagnose and therapy development.
