James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine 600 N Wolfe St., Baltimore, MD 21287, USA.
Curr Med Chem. 2011;18(27):4206-14. doi: 10.2174/092986711797189600.
Aptamers are a special class of nucleic acid molecules that are beginning to be investigated for clinical use. These small RNA/DNA molecules can form secondary and tertiary structures capable of specifically binding proteins or other cellular targets; they are essentially a chemical equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small in size, and non-immunogenic. Since the discovery of aptamers in the early 1990s, great efforts have been made to make them clinically relevant for diseases like cancer, HIV, and macular degeneration. In the last two decades, many aptamers have been clinically developed as inhibitors for targets such as vascular endothelial growth factor (VEGF) and thrombin. The first aptamer based therapeutic was FDA approved in 2004 for the treatment of age-related macular degeneration and several other aptamers are currently being evaluated in clinical trials. With advances in targeted-therapy, imaging, and nanotechnology, aptamers are readily considered as potential targeting ligands because of their chemical synthesis and ease of modification for conjugation. Preclinical studies using aptamer-siRNA chimeras and aptamer targeted nanoparticle therapeutics have been very successful in mouse models of cancer and HIV. In summary aptamers are in several stages of development, from pre-clinical studies to clinical trials and even as FDA approved therapeutics. In this review, we will discuss the current state of aptamers in clinical trials as well as some promising aptamers in pre-clinical development.
适配子是一类特殊的核酸分子，目前正开始被研究用于临床应用。这些小分子 RNA/DNA 分子能够形成二级和三级结构，能够特异性地结合蛋白质或其他细胞靶标；它们本质上是抗体的化学等价物。适配子具有高度特异性、相对较小的尺寸和非免疫原性的优势。自 20 世纪 90 年代初发现适配子以来，人们做出了巨大努力，以使它们在癌症、HIV 和黄斑变性等疾病的临床应用中具有相关性。在过去的二十年中，许多适配子已被开发为针对血管内皮生长因子 (VEGF) 和凝血酶等靶点的抑制剂。第一个基于适配子的治疗药物于 2004 年获得 FDA 批准，用于治疗年龄相关性黄斑变性，目前还有其他几种适配子正在临床试验中进行评估。随着靶向治疗、成像和纳米技术的进步，适配子因其易于化学合成和修饰用于缀合而被认为是潜在的靶向配体。在癌症和 HIV 的小鼠模型中，使用适配子-siRNA 嵌合体和适配子靶向纳米颗粒治疗的临床前研究非常成功。总之，适配子正处于从临床前研究到临床试验甚至作为 FDA 批准的治疗药物的几个不同的发展阶段。在这篇综述中，我们将讨论适配子在临床试验中的现状以及一些在临床前开发中很有前途的适配子。
