Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.
Institute of Nano Science and Technology, Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
J Control Release. 2021 Mar 10;331:121-141. doi: 10.1016/j.jconrel.2021.01.014. Epub 2021 Jan 13.
Gene therapy using nucleic acids has many clinical applications for the treatment of diseases with a genetic origin as well as for the development of innovative vaccine formulations. Since nucleic acids in their free form are rapidly degraded by nucleases present in extracellular matrices, have poor pharmacokinetics and hardly pass cellular membranes, carrier systems are required. Suitable carriers that protect the nucleic acid payload against enzymatic attack, prolong circulation time after systemic administration and assist in cellular binding and internalization are needed to develop nucleic acid based drug products. Viral vectors have been investigated and are also clinically used as delivery vehicles. However, some major drawbacks are associated with their use. Therefore there has been substantial attention on the use of non-viral carrier systems based on cationic lipids and polymers. This review focuses on the properties of polymer-based nucleic acid formulations, also referred as polyplexes. Different polymeric systems are summarized, and the cellular barriers polyplexes encounter and ways to tackle these are discussed. Finally attention is given to the clinical status of non-viral nucleic acid formulations.
基因治疗使用核酸具有许多临床应用，可用于治疗具有遗传起源的疾病，以及开发创新的疫苗制剂。由于游离形式的核酸在细胞外基质中存在的核酸酶的作用下迅速降解，具有较差的药代动力学特性，几乎不能穿透细胞膜，因此需要载体系统。需要合适的载体来保护核酸有效负载免受酶的攻击，延长全身给药后的循环时间，并有助于细胞结合和内化，以开发基于核酸的药物产品。病毒载体已被研究并也被临床用作递送载体。然而，它们的使用存在一些主要的缺点。因此，人们对基于阳离子脂质体和聚合物的非病毒载体系统的使用给予了极大的关注。本文重点介绍了基于聚合物的核酸制剂（也称为多聚物）的特性。总结了不同的聚合体系，并讨论了多聚物所遇到的细胞屏障和解决这些问题的方法。最后，关注了非病毒核酸制剂的临床现状。
