Becker Kristian C D, Becker Richard C
Boston University, College of Arts and Sciences, 725 Commonwealth Avenue, Boston, MA 02215, USA.
Curr Opin Mol Ther. 2006 Apr;8(2):122-9.
Nucleic acid 'aptamers', a term derived from the Latin word aptus, 'to fit', are RNA or DNA oligonucleotides that conform to the three-dimensional structure of a selected protein, peptide or small molecules' functional moiety. The 'lock and key' relationship between aptamers and their binding partner permits distinction between closely related but non-identical members of a protein family, or between different functional or conformational states of the same protein. This, along with other properties, separates aptamers from antibodies--the most popular class of molecular recognition tool for the past three decades. Despite the chemical, biological and manufacturing advantages offered by nucleic acid aptamers in a wide variety of conditions, and their generation against a range of clinically relevant targets, including growth factors, transcription factors and coagulation proteins, by two dozen or more companies devoted to the technology platform, only one aptamer, developed for the treatment of wet age-related macular degeneration, is currently available for use in humans. Nevertheless, phase I and II clinical trials for several indications are proceeding with considerable enthusiasm. The potential application of nucleic acid aptamers in novel arenas, including molecular imaging, vaccine development, immunomodulation, decoys for natural RNA-binding events, antiviral therapeutics and both cancer prophylaxis and treatment, is emerging with a pioneering mentality destined to change the paradigm of patient care.
核酸“适配体”一词源于拉丁语aptus，意为“适合”，是指能与选定蛋白质、肽或小分子功能部分的三维结构相契合的RNA或DNA寡核苷酸。适配体与其结合伴侣之间的“锁钥”关系，使得能够区分蛋白质家族中密切相关但并不相同的成员，或者同一蛋白质的不同功能或构象状态。这一点以及其他特性，将适配体与抗体区分开来——抗体是过去三十年里最受欢迎的一类分子识别工具。尽管核酸适配体在多种条件下具有化学、生物学及生产方面的优势，并且有二十多家专注于该技术平台的公司针对一系列临床相关靶点（包括生长因子、转录因子和凝血蛋白）研发出了适配体，但目前仅有一种用于治疗湿性年龄相关性黄斑变性的适配体可用于人体。尽管如此，针对多种适应症的I期和II期临床试验正在积极推进。核酸适配体在包括分子成像、疫苗研发、免疫调节、天然RNA结合事件的诱饵、抗病毒治疗以及癌症预防和治疗等新领域的潜在应用，正以一种开创性的思维方式崭露头角，注定会改变患者护理的模式。
