Current preclinical small interfering RNA (siRNA)-based conjugate systems for RNA therapeutics

被引：74

作者：

Lee, Soo Hyeon ^{[2
]}

Kang, Yoon Young ^{[1
]}

Jang, Hyo-Eun ^{[1
]}

Mok, Hyejung ^{[1
]}

机构：

[1] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea

[2] Swiss Fed Inst Technol Zurich ETHZ, Inst Pharmaceut Sci, Dept Chem & Appl Biosci, Zurich, Switzerland

来源：

ADVANCED DRUG DELIVERY REVIEWS | 2016年 / 104卷

关键词：

siRNA; Conjugate; Preclinical study; siRNA dose; Clinical translation; IN-VIVO DELIVERY; POLYELECTROLYTE COMPLEX MICELLES; CELL-PENETRATING PEPTIDES; APTAMER-SIRNA CHIMERAS; POLY(ETHYLENE GLYCOL)-SIRNA CONJUGATE; TARGETED DELIVERY; DRUG-DELIVERY; CANCER-CELLS; ASIALOGLYCOPROTEIN RECEPTOR; GOLD NANOPARTICLES;

D O I：

10.1016/j.addr.2015.10.009

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Recent promising clinical results of RNA therapeutics have drawn big attention of academia and industries to RNA therapeutics and their carrier systems. To improve their feasibility in clinics, systemic evaluations of currently available carrier systems under clinical trials and preclinical studies are needed. In this review, we focus on recent noticeable preclinical studies and clinical results regarding siRNA-based conjugates for clinical translations. Advantages and drawbacks of siRNA-based conjugates are discussed, compared to particle-based delivery systems. Then, representative siRNA-based conjugates with aptamers, peptides, carbohydrates, lipids, polymers, and nanostructured materials are introduced. To improve feasibility of siRNA conjugates in preclinical studies, several considerations for the rational design of siRNA conjugates in terms of cleavability, immune responses, multivalent conjugations, and mechanism of action are also presented. Lastly, we discuss lessons from previous preclinical and clinical studies related to siRNA conjugates and perspectives of their clinical applications. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：78 / 92

页数：15

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