Merkel Olivia M, Rubinstein Israel, Kissel Thomas
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA; Department of Oncology, Wayne State University, Detroit, MI 48201, USA.
College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
Adv Drug Deliv Rev. 2014 Aug;75:112-28. doi: 10.1016/j.addr.2014.05.018. Epub 2014 Jun 5.
RNA interference (RNAi) has been thought of as the general answer to many unmet medical needs. After the first success stories, it soon became obvious that short interfering RNA (siRNA) is not suitable for systemic administration due to its poor pharmacokinetics. Therefore local administration routes have been adopted for more successful in vivo RNAi. This paper reviews nucleic acid modifications, nanocarrier chemistry, animal models used in successful pulmonary siRNA delivery, as well as clinical translation approaches. We summarize what has been published recently and conclude with the potential problems that may still hamper the efficient clinical application of RNAi in the lung.
RNA干扰（RNAi）被认为是解决许多未满足医疗需求的通用方法。在首批成功案例出现后，很快就发现小干扰RNA（siRNA）由于其不良的药代动力学性质而不适合全身给药。因此，为了在体内更成功地实现RNAi，人们采用了局部给药途径。本文综述了核酸修饰、纳米载体化学、成功进行肺部siRNA递送所使用的动物模型以及临床转化方法。我们总结了最近发表的内容，并总结了可能仍然阻碍RNAi在肺部有效临床应用的潜在问题。
