title: Current preclinical small interfering RNA (siRNA)-based conjugate systems for RNA therapeutics.
abstract: 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.
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETHZ), Zurich, Switzerland.
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Kang
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyo-Eun
authors.initials: HE
authors.lastname: Jang
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: hjmok@konkuk.ac.kr.
authors.forename: Hyejung
authors.initials: H
authors.lastname: Mok
mesh_terms: D006801:Humans; D008055:Lipids; D049329:Nanostructures; D010455:Peptides; D011108:Polymers; D034622:RNA Interference; D034741:RNA, Small Interfering; D000067492:RNAi Therapeutics
chemical_list: D008055:Lipids; D010455:Peptides; D011108:Polymers; D034741:RNA, Small Interfering
keywords: Clinical translation; Conjugate; Preclinical study; siRNA; siRNA dose