Winkler Johannes
Department of Medicinal Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
Ther Deliv. 2011 Jul;2(7):891-905. doi: 10.4155/tde.11.56.
The enormous promise of siRNA technology for rational and targeted therapy can only be realized if the inherent problems in terms of pharmaceutical development are overcome. Besides liposomal and polymeric nanoparticles, fusion proteins hold great potential for cell-type specific delivery of siRNA. Consisting of a protein binder and an oligonucleotide complexing domain, fusion proteins are designed for targeted delivery to a certain tissue or organ and subsequent release of the siRNA after cellular uptake. This article focuses on the possibilities and importance of targeting and complexing domains, including polymers and dendrimers. In vitro and in vivo evaluations are discussed with an in-depth view on pharmacokinetic properties. Remaining challenges concerning specificity on the tissue and molecular levels are highlighted.
只有克服药物研发方面的固有问题，小干扰RNA（siRNA）技术用于合理且靶向治疗的巨大前景才能得以实现。除了脂质体和聚合物纳米颗粒外，融合蛋白在siRNA的细胞类型特异性递送方面具有巨大潜力。融合蛋白由蛋白质结合剂和寡核苷酸络合结构域组成，旨在靶向递送至特定组织或器官，并在细胞摄取后随后释放siRNA。本文重点关注靶向和络合结构域的可能性和重要性，包括聚合物和树枝状大分子。文中深入讨论了体外和体内评估以及药代动力学特性。突出了在组织和分子水平上关于特异性的 remaining challenges（原文此处“remaining challenges”表述有误，推测可能是“remaining challenges”，可译为“剩余挑战” ）。
