Hartmann G, Bidlingmaier M, Eigler A, Hacker U, Endres S
Medizinische Klinik, Klinikum Innenstadt of the Ludwig-Maximilians-University, Munich, Germany.
Cytokines Cell Mol Ther. 1997 Dec;3(4):247-56.
Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies.
治疗性寡核苷酸——合成核酸的短链——包括反义寡核苷酸和适体寡核苷酸。反义寡核苷酸旨在通过互补碱基配对与靶RNA结合，并抑制靶蛋白的翻译。反义寡核苷酸能够特异性抑制细胞因子的合成。相比之下，适体寡核苷酸能够直接与特定蛋白质结合。这种结合取决于寡核苷酸的序列。具有CpG基序的适体寡核苷酸可发挥强大的免疫刺激作用。反义寡核苷酸和适体寡核苷酸这两种治疗性寡核苷酸都为调节免疫功能提供了有前景的工具。最近，治疗性寡核苷酸已走向临床应用。一种针对促炎细胞间黏附分子1（ICAM-1）的反义寡核苷酸目前正在进行治疗炎症性疾病的临床试验。免疫刺激适体寡核苷酸正处于免疫治疗的临床前开发阶段。在本综述中，我们总结了治疗性寡核苷酸在调节免疫功能方面的应用。我们涵盖了技术方面以及当前的治疗概念和临床研究。
