RNAi 疗法：拓展到肝外疾病的应用和克服递药挑战。
RNAi therapies: Expanding applications for extrahepatic diseases and overcoming delivery challenges.
机构信息
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea; Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
出版信息
Adv Drug Deliv Rev. 2023 Oct;201:115073. doi: 10.1016/j.addr.2023.115073. Epub 2023 Aug 30.
The era of RNA medicine has become a reality with the success of messenger RNA (mRNA) vaccines against COVID-19 and the approval of several RNA interference (RNAi) agents in recent years. Particularly, therapeutics based on RNAi offer the promise of targeting intractable and previously undruggable disease genes. Recent advances have focused in developing delivery systems to enhance the poor cellular uptake and insufficient pharmacokinetic properties of RNAi therapeutics and thereby improve its efficacy and safety. However, such approach has been mainly achieved via lipid nanoparticles (LNPs) or chemical conjugation with N-Acetylgalactosamine (GalNAc), thus current RNAi therapy has been limited to liver diseases, most likely to encounter liver-targeting limitations. Hence, there is a huge unmet medical need for intense evolution of RNAi therapeutics delivery systems to target extrahepatic tissues and ultimately extend their indications for treating various intractable diseases. In this review, challenges of delivering RNAi therapeutics to tumors and major organs are discussed, as well as their transition to clinical trials. This review also highlights innovative and promising preclinical RNAi-based delivery platforms for the treatment of extrahepatic diseases.
RNA 药物时代已经成为现实，随着针对 COVID-19 的信使 RNA（mRNA）疫苗的成功以及近年来几种 RNA 干扰（RNAi）药物的批准。特别是，基于 RNAi 的疗法有望针对难治性和以前无法治疗的疾病基因。最近的进展集中在开发输送系统上，以增强 RNAi 疗法的细胞摄取不良和药代动力学性质不足，并提高其疗效和安全性。然而，这种方法主要是通过脂质纳米粒（LNPs）或与 N-乙酰半乳糖胺（GalNAc）的化学缀合来实现的，因此，目前的 RNAi 疗法仅限于肝脏疾病，很可能会遇到肝脏靶向限制。因此，迫切需要对 RNAi 疗法的输送系统进行深入的研究，以针对肝外组织，并最终扩大其治疗各种难治性疾病的适应症。在这篇综述中，讨论了将 RNAi 疗法递送到肿瘤和主要器官的挑战，以及它们向临床试验的转化。这篇综述还强调了用于治疗肝外疾病的创新和有前途的基于 RNAi 的临床前输送平台。
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