Dokka S, Rojanasakul Y
West Virginia University, Department of Basic Pharmaceutical Sciences, School of Pharmacy, P.O. Box 9530, Morgantown, WV 26506, USA.
Adv Drug Deliv Rev. 2000 Oct 31;44(1):35-49. doi: 10.1016/s0169-409x(00)00082-x.
Antisense oligonucleotides (ONs) have several properties that make them attractive as therapeutic agents. Hybridization of antisense ONs to their complementary nucleic acid sequences by Watson-Crick base pairing is a highly selective and efficient process. Design of therapeutic antisense agents can be made more rationally as compared to most traditional drugs, i.e., they can be designed on the basis of target RNA sequences and their secondary structures. Despite these advantages, the design and use of antisense ONs as therapeutic agents are still faced with several obstacles. One major obstacle is their inefficient cellular uptake and poor accessibility to target sites. In this article, we will discuss key barriers affecting ON delivery and approaches to overcome these barriers. Current methods of ON delivery will be reviewed with an emphasis on novel non-endocytic methods of delivery. ONs are taken up by cells via an endocytic process. The process of ON release from endosomes is a very inefficient process and, hence, ONs end up being degraded in the endosomes. Thus, ONs do not reach their intended site of action in the cytoplasm or nucleus. Delivery systems ensuring a cytoplasmic delivery of ONs have the potential to increase the amount of ON reaching the target. Here, we shall examine various ON delivery methods that bypass the endosomal pathway. The advantages and disadvantages of these methods compared to other existing methods of ON delivery will be discussed.
反义寡核苷酸（ONs）具有多种特性，使其作为治疗剂具有吸引力。反义ONs通过沃森-克里克碱基配对与其互补核酸序列杂交是一个高度选择性和高效的过程。与大多数传统药物相比，治疗性反义药物的设计可以更合理，也就是说，可以基于靶RNA序列及其二级结构进行设计。尽管有这些优点，反义ONs作为治疗剂的设计和使用仍然面临几个障碍。一个主要障碍是它们细胞摄取效率低下且难以到达靶位点。在本文中，我们将讨论影响ON递送的关键障碍以及克服这些障碍的方法。将对当前的ON递送方法进行综述，重点是新型非内吞递送方法。ONs通过内吞过程被细胞摄取。ON从内体释放的过程是一个非常低效的过程，因此，ON最终会在内体中被降解。因此，ON无法到达其在细胞质或细胞核中的预期作用位点。确保ON细胞质递送的递送系统有可能增加到达靶标的ON量。在这里，我们将研究绕过内体途径的各种ON递送方法。将讨论这些方法与其他现有ON递送方法相比的优缺点。
