Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA.
Adv Drug Deliv Rev. 2018 Sep;134:65-78. doi: 10.1016/j.addr.2018.08.005. Epub 2018 Aug 17.
Precision medicine holds great promise to harness genetic and epigenetic cues for targeted treatment of a variety of diseases, ranging from many types of cancers, neurodegenerative diseases, to cardiovascular diseases. The proteomic profiles resulting from the unique genetic and epigenetic signatures represent a class of relatively well accessible molecular targets for both interrogation (e.g., diagnosis, prognosis) and intervention (e.g., targeted therapy) of these diseases. Aptamers are promising for such applications by specific binding with cognate disease biomarkers. Nucleic acid aptamers are a class of DNA or RNA with unique three-dimensional conformations that allow them to specifically bind with target molecules. Aptamers can be relatively easily screened, reproducibly manufactured, programmably designed, and chemically modified for various biomedical applications, including targeted therapy. Aptamers can be chemically modified to resist enzymatic degradation or optimize their pharmacological behaviors, which ensured their chemical integrity and bioavailability under physiological conditions. In this review, we will focus on recent progress and discuss the challenges and opportunities in the research areas of aptamer-based targeted therapy in the forms of aptamer therapeutics and aptamer-drug conjugates (ApDCs).
精准医学有望利用遗传和表观遗传线索，针对多种疾病进行靶向治疗，这些疾病范围广泛，包括多种癌症、神经退行性疾病和心血管疾病。源自独特遗传和表观遗传特征的蛋白质组特征代表了一类相对容易获得的分子靶点，可用于这些疾病的检测（例如，诊断、预后）和干预（例如，靶向治疗）。适体通过与同源疾病生物标志物的特异性结合，在这些应用中具有广阔的应用前景。核酸适体是一类具有独特三维构象的 DNA 或 RNA，使其能够特异性地与靶分子结合。适体可以相对容易地筛选、可重复地制造、可编程地设计和化学修饰，用于各种生物医学应用，包括靶向治疗。适体可以进行化学修饰以抵抗酶降解或优化其药理行为，从而确保其在生理条件下的化学完整性和生物利用度。在这篇综述中，我们将重点介绍最新进展，并讨论基于适体的靶向治疗在适体治疗和适体-药物偶联物（ApDCs）形式中的研究领域的挑战和机遇。
